284 results
Search Results
202. Efficacy of interventions to combat tobacco addiction: <scp>C</scp> ochrane update of 2012 reviews
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Kate Cahill, Jamie Hartmann-Boyce, Tim Lancaster, and Lindsay F Stead
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medicine.medical_specialty ,media_common.quotation_subject ,medicine.medical_treatment ,education ,Psychological intervention ,Medicine (miscellaneous) ,chemistry.chemical_compound ,Alkaloids ,Pharmacotherapy ,Meta-Analysis as Topic ,Behavior Therapy ,Quinoxalines ,medicine ,Humans ,Nicotinic Agonists ,Varenicline ,Psychiatry ,media_common ,business.industry ,Addiction ,Smoking ,Tobacco Use Disorder ,Benzazepines ,Nicotine replacement therapy ,Azocines ,Behavior, Addictive ,Review Literature as Topic ,Psychiatry and Mental health ,Treatment Outcome ,Systematic review ,chemistry ,Family medicine ,Relative risk ,Smoking cessation ,Smoking Cessation ,business ,Quinolizines - Abstract
Background and aims: The Cochrane Collaboration is an international not-for-profit organization which produces and disseminates systematic reviews of health-care interventions. This paper is the first in a series of annual updates of Cochrane reviews on tobacco addiction interventions. It also provides an up-to-date overview of review findings in this area to date and summary statistics for cessation reviews in which meta-analyses were conducted. Methods: In 2012, the Group published seven new reviews and updated 13 others. This update summarizes and comments on these reviews. It also summarizes key findings from all the other reviews in this area. Results: New reviews in 2012 found that in smokers using pharmacotherapy, behavioural support improves success rates [risk ratio (RR) 1.16, 95% confidence interval (CI)=1.09-1.24], and that combining behavioural support and pharmacotherapy aids cessation (RR 1.82, 95% CI=1.66-2.00). Updated reviews established mobile phones as potentially helpful in aiding cessation (RR 1.71, 95% CI=1.47-1.99), found that cytisine (RR 3.98, 95% CI=2.01-7.87) and low-dose varenicline (RR 2.09, 95% CI=1.56-2.78) aid smoking cessation, and found that training health professionals in smoking cessation improves patient cessation rates (RR 1.60, 95% CI=1.26-2.03). The updated reviews confirmed the benefits of nicotine replacement therapy, standard dose varenicline and providing cessation treatment free of charge. Lack of demonstrated efficacy remained for partner support, expired-air carbon monoxide feedback and lung function feedback. Conclusions: Cochrane systematic review evidence for the first time establishes the efficacy of behavioural support over and above pharmacotherapy, as well as the efficacy of cytisine, mobile phone technology, low-dose varenicline and health professional training in promoting smoking cessation. © 2013 ociety for the Study of Addiction.
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- 2013
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203. Is Heart Rate a Norepiphenomenon in Heart Failure?
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J O’Neill and Mark Hensey
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Adrenergic Antagonists ,Digoxin ,medicine.medical_specialty ,Amiodarone ,Disease ,030204 cardiovascular system & hematology ,RESTING HEART RATE ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Humans ,Ivabradine ,030212 general & internal medicine ,Heart Failure ,Evidence-Based Medicine ,business.industry ,Benzazepines ,medicine.disease ,Depression, Chemical ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business - Abstract
There has been an increased focus on heart rate as a target in the management of cardiovascular disease and more specifically in heart failure with preserved ejection fraction in recent years with several studies showing the benefit of a lower resting heart rate on outcomes. This review paper examines the pathophysiology behind the benefits of lowering heart rate in heart failure and also the evidence for and against the pharmacological agents available to achieve this.
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- 2016
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204. Ivabradine: A Review of Labeled and Off-Label Uses
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Carrie S. Oliphant, Oluwaseyi Bolorunduro, Ryan E. Owens, and Sunil K. Jha
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medicine.medical_specialty ,medicine.drug_class ,Adrenergic beta-Antagonists ,Blood Pressure ,030204 cardiovascular system & hematology ,Coronary artery disease ,Angina ,03 medical and health sciences ,0302 clinical medicine ,Heart Rate ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Ivabradine ,030212 general & internal medicine ,Beta blocker ,Clinical Trials as Topic ,business.industry ,Atrial fibrillation ,Cardiovascular Agents ,General Medicine ,Off-Label Use ,Benzazepines ,medicine.disease ,Inappropriate sinus tachycardia ,Clinical trial ,Cardiovascular Diseases ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data.
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- 2016
205. Safety of Varenicline Among Smokers Enrolled in the Lung HIV Study
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Philip T. Diaz, Susan L. Koletar, Amy K. Ferketich, Mary Ellen Wewers, Kristine K. Browning, Nancy R. Reynolds, and Bo Lu
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Adult ,Male ,Nicotine ,medicine.medical_specialty ,media_common.quotation_subject ,medicine.medical_treatment ,Population ,HIV Infections ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,Telephone counseling ,law ,Quinoxalines ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,Varenicline ,Prospective cohort study ,education ,Original Investigation ,media_common ,education.field_of_study ,business.industry ,Public Health, Environmental and Occupational Health ,Benzazepines ,Middle Aged ,Abstinence ,Nicotine replacement therapy ,Surgery ,Treatment Outcome ,chemistry ,behavior and behavior mechanisms ,Smoking cessation ,Female ,Smoking Cessation ,business - Abstract
INTRODUCTION The prevalence of smoking is high among the human immunodeficiency virus (HIV)-infected population, yet there are few studies of tobacco dependence treatment in this population. This paper reports the safety of varenicline versus nicotine replacement therapy (NRT) and describes preliminary results about the effectiveness of varenicline versus NRT in HIV-infected smokers. METHODS Participants completed 12 weeks of telephone counseling and either varenicline or NRT. Varenicline was encouraged as the preferred intervention; NRT was used for those unable/unwilling to take varenicline. Adverse events (AEs), related to pharmacotherapy, were monitored. Biochemically confirmed abstinence at 3 months was examined. Inverse probability of treatment weighted logistic regression models was fit to compare participants on varenicline to those on NRT. RESULTS Among participants on varenicline (n = 118), the most common AEs were nausea, sleep problems, and mood disturbances. One person reported suicidal ideation; there were no cardiovascular complications. There were no differences in the varenicline AE profile between participants on combination antiretroviral therapy (ART) and those not on ART. The percentages of confirmed abstainers were 11.8% in the NRT group and 25.6% in the varenicline group. The odds of being abstinent were 2.54 times as great in the varenicline group compared with the NRT group in the propensity weighted model (95% CI 1.43-4.49). CONCLUSIONS In this preliminary study, the safety profile of varenicline among HIV-infected smokers resembles findings among smokers without HIV. In addition, varenicline may be more effective at promoting abstinence in this population. Future randomized clinical trials are warranted.
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- 2012
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206. Concomitant Administration of Different Doses of Simvastatin with Ivabradine Influence on PAI-1 and Heart Rate in Normo- and Hypercholesterolaemic Rats
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Jacek Owczarek, Daria Orszulak-Michalak, and Magdalena Jasińska-Stroschein
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Male ,Simvastatin ,medicine.medical_specialty ,Article Subject ,Hypercholesterolemia ,lcsh:Medicine ,Blood Pressure ,Pharmacology ,lcsh:Technology ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Heart Rate ,Risk Factors ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Heart rate ,medicine ,Animals ,Ivabradine ,Rats, Wistar ,lcsh:Science ,General Environmental Science ,Models, Statistical ,lcsh:T ,Cholesterol ,business.industry ,lcsh:R ,Cardiovascular Agents ,General Medicine ,Benzazepines ,Lipids ,Rats ,Endocrinology ,Blood pressure ,chemistry ,Plasminogen activator inhibitor-1 ,Concomitant ,Cardiovascular agent ,lcsh:Q ,Acyl Coenzyme A ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Research Article ,medicine.drug - Abstract
Ivabradine is a novel heart rate lowering agent that inhibits Ifionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and20 mg×kg−1 bw) with ivabradine (10 mg×kg−1 bw) during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving20 mg×kg−1 bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of20 mg×kg−1 bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone.Conclusion.The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders.
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- 2012
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207. Mechanism-Based Therapeutics for Autosomal Dominant Polycystic Kidney Disease: Recent Progress and Future Prospects
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Albert C.M. Ong and Ming-Yang Chang
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Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Tolvaptan ,Autosomal dominant polycystic kidney disease ,Cystic Fibrosis Transmembrane Conductance Regulator ,Bioinformatics ,Translational Research, Biomedical ,Double-Blind Method ,Nitriles ,Cyclic AMP ,Roscovitine ,medicine ,Polycystic kidney disease ,Humans ,Multicenter Studies as Topic ,Renal replacement therapy ,Disease management (health) ,Antihypertensive Agents ,Randomized Controlled Trials as Topic ,Clinical Trials as Topic ,Aniline Compounds ,PKD1 ,business.industry ,TOR Serine-Threonine Kinases ,Disease Management ,Drugs, Investigational ,General Medicine ,Benzazepines ,Polycystic Kidney, Autosomal Dominant ,medicine.disease ,Histone Deacetylase Inhibitors ,Clinical trial ,Purines ,Nephrology ,Depression, Chemical ,Quinolines ,Somatostatin ,business ,Forecasting ,Signal Transduction ,medicine.drug ,Kidney disease - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, accounting for up to 10% of patients on renal replacement therapy. There are presently no proven treatments for ADPKD and an effective disease-modifying drug would have significant implications for patients and their families. Since the identification of PKD1 and PKD2, there has been an explosion in knowledge identifying new disease mechanisms and testing new drugs. Currently, the three major treatment strategies are to: (1) reduce cAMP levels; (2) inhibit cell proliferation, and (3) reduce fluid secretion. Several compounds shown to be effective in preclinical models have already undergone clinical trials and more are planned. In addition, a whole raft of other compounds have been developed from preclinical studies. The purpose of this paper is to evaluate the results of recent published trials, review current trials and highlight the most promising compounds in the pipeline. There appears to be no shortage of potential candidates, but several key issues need to be addressed to facilitate clinical translation.
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- 2011
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208. Impact of symptoms experienced by varenicline users on tobacco treatment in a real world setting
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Susan M. Zbikowski, Sheryl L. Catz, Julie Richards, T. Mona Deprey, Lisa M. Jack, Jennifer B. McClure, Timothy A. McAfee, Abigail C. Halperin, and Gary E. Swan
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Side effect ,Nausea ,medicine.medical_treatment ,Medicine (miscellaneous) ,Smoking Prevention ,Receptors, Nicotinic ,Article ,law.invention ,chemistry.chemical_compound ,Sex Factors ,Telephone counseling ,Randomized controlled trial ,Recurrence ,law ,Quinoxalines ,medicine ,Humans ,Nicotinic Agonists ,Psychiatry ,Varenicline ,Internet ,Cognitive Behavioral Therapy ,business.industry ,Benzazepines ,Middle Aged ,Combined Modality Therapy ,Telephone ,Discontinuation ,Psychiatry and Mental health ,Clinical Psychology ,chemistry ,Cognitive therapy ,Smoking cessation ,Female ,Smoking Cessation ,Pshychiatric Mental Health ,medicine.symptom ,business - Abstract
This paper examines reported symptoms, nonsmoking rates, and medication use among 1018 smokers using varenicline in a randomized trial comparing three forms of behavioral support for smoking cessation (phone, web, or phone + web). One month after beginning varenicline, 168 people (17%) had discontinued the medication. Most (53%) quit due to side-effects and other symptoms. The most common side-effect among all users was nausea (reported by 57% of users). At one month post medication initiation, those not taking varenicline were more likely to report smoking than those who continued the medication (57% vs. 16%, p
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- 2009
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209. EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan
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Sadiya S. Khan, Mihai Gheorghiade, and João L. Cavalcante
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Male ,Vasopressin ,medicine.medical_specialty ,medicine.drug_class ,Tolvaptan ,Renal function ,Edema ,Internal Medicine ,medicine ,Humans ,Intensive care medicine ,Aged ,Randomized Controlled Trials as Topic ,Heart Failure ,business.industry ,Cardiovascular Agents ,General Medicine ,Emergency department ,Benzazepines ,Middle Aged ,medicine.disease ,Europe ,Hospitalization ,Heart failure ,Acute Disease ,North America ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Hyponatremia ,business ,Antidiuretic Hormone Receptor Antagonists ,Vasopressin Antagonists ,medicine.drug - Abstract
Acute heart failure syndromes are a common cause of emergency department visits and hospitalization in North America and Europe. Although in-hospital mortality is relatively low, the postdischarge mortality and rehospitalization rates can be as high as 10-15 and 30%, respectively, within 60-90 days following discharge. It appears that the main reason for admission and readmission for heart failure is related to congestion manifested by dyspnea, jugular venous distension and edema. Often, congestion is associated with dilutional hyponatremia that is difficult to treat. Hyponatremia is an important predictor of increased mortality and the available therapies to treat congestion and/or hyponatremia are often ineffective and/or unsafe. Accordingly, there is an unmet need to develop a new agent that effectively relieves congestion due to high filling pressure without worsening renal function and improving or normalizing serum sodium in hyponatremic patients. This paper provides an overview of a new compound, tolvaptan, an oral selective V(2)-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. The biochemical and pharmacological properties are discussed in conjunction with its clinical efficacy and safety, exploring the potential role of tolvaptan in the management of acute heart failure syndromes presenting with or without hyponatremia.
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- 2008
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210. V2receptor antagonism with tolvaptan in heart failure
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John C. Burnett, Guido Boerrigter, and Lisa C. Costello-Boerrigter
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medicine.medical_specialty ,Vasopressin ,Tolvaptan ,Pharmacology ,Aquaretic ,Internal medicine ,Arginine vasopressin receptor 2 ,Animals ,Humans ,Medicine ,Pharmacology (medical) ,Diuretics ,Receptor ,Vasopressin receptor ,Heart Failure ,Clinical Trials as Topic ,business.industry ,Reabsorption ,General Medicine ,Benzazepines ,medicine.disease ,Arginine Vasopressin ,Endocrinology ,Heart failure ,business ,Antidiuretic Hormone Receptor Antagonists ,medicine.drug - Abstract
The prevalence and incidence of congestive heart failure continues to increase. The two hallmarks of this syndrome, sodium and water retention, are frequently a therapeutic challenge. Most conventional diuretics act primarily as saluretics by inhibiting renal tubular electrolyte reabsorption, which, due to osmotic pressure, promotes excretion of isotonic fluid. The peptide hormone arginine vasopressin vasoconstricts at the V(1A) receptor and promotes water reabsorption via the V(2) receptor in the renal collecting duct by inserting aquaporin-2 water channels into the luminal membrane. Tolvaptan, the first orally available non-peptide V(2) receptor antagonist, acts as a potent aquaretic. In this paper, the authors review the pharmacology of tolvaptan and discuss the results of the initial clinical trials with this potent new drug.
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- 2007
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211. Neurosteroid dehydroepiandrosterone sulfate enhances spontaneous glutamate release in rat prelimbic cortex through activation of dopamine D1 and sigma-1 receptor
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Ping Zheng, Ying-Mei Fu, Zemin Wang, Yan-Hua Zhu, Lian-Yan Dong, Jianli Sun, Zheng-Xiang Cheng, and Yi Dong
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medicine.medical_specialty ,Patch-Clamp Techniques ,medicine.drug_class ,Infralimbic cortex ,Glutamic Acid ,Hippocampus ,In Vitro Techniques ,Membrane Potentials ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Dopamine receptor D1 ,Dehydroepiandrosterone sulfate ,Internal medicine ,medicine ,Animals ,Receptors, sigma ,Drug Interactions ,Enzyme Inhibitors ,Protein kinase A ,Cerebral Cortex ,Pharmacology ,Sigma-1 receptor ,Dose-Response Relationship, Drug ,Dehydroepiandrosterone Sulfate ,Receptors, Dopamine D1 ,Glutamate receptor ,Excitatory Postsynaptic Potentials ,Benzazepines ,Receptor antagonist ,Cyclic AMP-Dependent Protein Kinases ,Rats ,Pyrimidines ,Endocrinology ,medicine.anatomical_structure ,Animals, Newborn ,chemistry ,Dopamine Antagonists ,Imines ,Synaptosomes - Abstract
This paper studied the effect of neurosteroid dehydroepiandrosterone sulfate on spontaneous glutamate release in the prelimbic cortex by using electrophysiological and biochemical methods combined with a pharmacological approach and made some comparisons with those in the hippocampus. The results showed that dehydroepiandrosterone sulfate increased the frequency of miniature excitatory postsynaptic currents in the prelimbic cortex and hippocampus; sigma-1 receptor antagonist partially blocked the effect of dehydroepiandrosterone sulfate in the prelimbic cortex, but completely blocked it in the hippocampus; D1 receptor antagonist, adenylyl cyclase inhibitor and protein kinase A inhibitor completely blocked the effect of dehydroepiandrosterone sulfate in the prelimbic cortex; dehydroepiandrosterone sulfate increased the activity of protein kinase A in the prelimbic cortex and hippocampus; the effect of dehydroepiandrosterone sulfate on protein kinase A was completely blocked by sigma-1 receptor antagonist in the hippocampus, but was partially blocked in the prelimbic cortex; interestingly, here again, the effect of dehydroepiandrosterone sulfate on protein kinase A was completely blocked by D1 receptor antagonist in the prelimbic cortex. These results suggest that dehydroepiandrosterone sulfate promotes presynaptic glutamate release in the prelimbic cortex via activation of D1 and sigma-1 receptors.
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- 2007
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212. A common mechanism allows selective targeting of GluN2B subunit-containing N-methyl-D-aspartate receptors.
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Schreiber, Julian A., Schepmann, Dirk, Frehland, Bastian, Thum, Simone, Datunashvili, Maia, Budde, Thomas, Hollmann, Michael, Strutz-Seebohm, Nathalie, Wünsch, Bernhard, and Seebohm, Guiscard
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METHYL aspartate receptors ,NEURODEGENERATION ,CELL death ,BENZAZEPINES ,STRUCTURAL models - Abstract
N-methyl-D-aspartate receptors (NMDARs), especially GluN2B-containing NMDARs, are associated with neurodegenerative diseases like Parkinson, Alzheimer and Huntington based on their high Ca
2+ conductivity. Overactivation leads to high intracellular Ca2+ concentrations and cell death rendering GluN2B-selective inhibitors as promising drug candidates. Ifenprodil represents the first highly potent prototypical, subtype-selective inhibitor of GluN2B-containing NMDARs. However, activity of ifenprodil on serotonergic, adrenergic and sigma receptors limits its therapeutic use. Structural reorganization of the ifenprodil scaffold to obtain 3-benzazepines retained inhibitory GluN2B activity but decreased the affinity at the mentioned non-NMDARs. While scaffold optimization improves the selectivity, the molecular inhibitory mechanism of these compounds is still not known. Here, we show a common inhibitory mechanism of ifenprodil and the related 3-benzazepines by mutational modifications of the receptor binding site, chemical modifications of the 3-benzazepine scaffold and subsequent in silico simulation of the inhibitory mechanism. Schreiber et al characterize a common inhibitory mechanism for ifenprodil and its derived compounds acting on GluN2B-containing N-methyl-D-aspartate receptors (NMDARs). These insights, generated through mutagenesis of the receptor binding site, chemical modifications of the compounds and structural modeling, may aid in the treatment of neurodegenerative diseases where GluN2B is involved. [ABSTRACT FROM AUTHOR]- Published
- 2019
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213. Infusion of neuropeptide Y into CA3 region of hippocampus produces antidepressant-like effect via Y1 receptor
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Kazuyuki Nakagome, Ryuzou Kawahara, Masaaki Iwata, Hisahito Ishida, Seiji Katayama, Yukihiko Shirayama, and Ayaka Yamamoto
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Male ,Receptors, Neuropeptide ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Cognitive Neuroscience ,Hippocampus ,Learned helplessness ,Arginine ,Receptors, G-Protein-Coupled ,Antidepressant like ,Rats, Sprague-Dawley ,Helplessness, Learned ,Internal medicine ,mental disorders ,Avoidance Learning ,Reaction Time ,medicine ,Animals ,Drug Interactions ,Neuropeptide Y ,Peptide YY ,Injections, Intraventricular ,Behavior, Animal ,Dose-Response Relationship, Drug ,Depression ,Chemistry ,Dentate gyrus ,Antagonist ,Benzazepines ,Neuropeptide Y receptor ,Antidepressive Agents ,humanities ,Rats ,Disease Models, Animal ,Endocrinology ,nervous system ,Exploratory Behavior ,Y1 receptor ,Neuroscience - Abstract
A couple of papers indicate that patients with depression show a decrease in serum neuropeptide Y (NPY). To study the role of NPY in depression, we examined the effects of infusion of NPY into the hippocampus of learned helplessness (LH) rats (an animal model of depression). Infusion of NPY into the cerebral ventricle of LH rats showed antidepressant-like effects. Infusion of NPY into the CA3 region, but not the dentate gyrus (DG), produced antidepressant-like effects in the LH paradigm. Infusion of NPY did not affect locomotor activity or aversive learning ability. Coadministration of BIBO3304 (a Y1 receptor antagonist) with NPY to the CA3 region blocked the antidepressant-like effects of NPY, whereas coadministration of NPY with BIIE0246 (a Y2 receptor antagonist) to the CA3 region failed to block antidepressant-like effects. Furthermore, infusions of [Leu31 Pro34]PYY (a Y1 and Y5 receptor agonist) alone and BIIE0246 alone into the CA3 region produced the antidepressant-like effects in LH rats. These results suggest that infusion of NPY into the CA3 region of hippocampus of LH rats produces antidepressant-like activity through Y1 receptors and attenuating effects through Y2 receptors. © 2007 Wiley-Liss, Inc.
- Published
- 2007
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214. Distinguishing rotamers in N-trifluoroacetyl-3-benzazepine derivatives
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Williams A, Acevedo-Fuentes and Bruce K, Cassels
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Carbon Isotopes ,Isomerism ,Receptors, Serotonin ,Appetite Depressants ,Thermodynamics ,Fluorine ,Benzazepines ,Carbon-13 Magnetic Resonance Spectroscopy ,Oxidation-Reduction ,Serotonin Receptor Agonists - Abstract
This paper provides the full (13) C NMR assignments for the trifluoroacetamides of five potentially appetite-reducing 5-HT2C benzazepine receptor agonists and two open-ring synthetic precursors. These compounds exist in solution as mixtures of two rotamers for each of which the (13) C NMR signals have now been assigned with the assistance of 2D NMR experiments and the carbonyl-induced shifts of the neighboring (13) CH2 resonances and long-range (13) C/(19) F couplings.
- Published
- 2015
215. Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat
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Trevor W. Robbins and Keith Matthews
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Adult ,Narcotics ,Dextroamphetamine ,Cognitive Neuroscience ,Vulnerability ,Differential Threshold ,Developmental psychology ,Behavioral Neuroscience ,Self Stimulation ,Reward ,medicine ,Animals ,Humans ,Social isolation ,Depression (differential diagnoses) ,Analysis of Variance ,Maternal deprivation ,Behavior, Animal ,Depression ,Maternal Deprivation ,Medial Forebrain Bundle ,Anhedonia ,Cognition ,Benzazepines ,Electric Stimulation ,Rats ,Heroin ,Disease Models, Animal ,Neuropsychology and Physiological Psychology ,Raclopride ,Etiology ,Conditioning, Operant ,Central Nervous System Stimulants ,Female ,medicine.symptom ,Psychology ,Psychomotor Performance ,Stress, Psychological ,Antipsychotic Agents ,Psychopathology - Abstract
Depression is a major public health concern, representing one of the most significant causes of disability and morbidity. Despite significant advances in the definition of specific cognitive, emotional and neural dysfunctions that are associated with depression, there has been frustratingly little progress in the elucidation of plausible aetiological and pathophysiological mechanisms. The complex, multi-system dysfunctions of depressive illness do not lend themselves to hypothesis-driven, systematic manipulation in patients. For this reason, there is a need to develop valid and reliable models of affective psychopathology in laboratory animals. In this paper, we review briefly some of our previous work demonstrating that a specific periodic neonatal maternal separation procedure leads to a robust constellation of behavioural changes in the adult rat that resemble core aspects of human depressive psychopathology. We also present data from a study of the adult effects of the same manipulation on electrical intracranial self-stimulation behaviour. These data further support the hypothesis that it is possible to model vulnerability to anhedonia in the adult rat by manipulation of early experience.
- Published
- 2003
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216. [Vareniklin: a safe treatment of tobacco dependency for cardiovascular patients]
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Alexandra, Kmeťová, Kamila, Zvolská, and Eva, Králíková
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Cardiovascular Diseases ,Risk Factors ,Quinoxalines ,Smoking ,Humans ,Smoking Cessation ,Nicotinic Agonists ,Tobacco Use Disorder ,Benzazepines ,Varenicline ,Risk Reduction Behavior - Abstract
Smoking is the leading risk factor for cardiovascular (CV) diseases. Eliminating exposure to tobacco smoke reduces CV risk in half. Tobacco dependence is similar to heroin addiction in its mechanisms and level of addictiveness or treatment success. Treatment includes both a change of daily stereotypes and pharmacotherapy. The most effective medication, varenicline, which depending on intensity of intervention triples the success rate, has been used since 2006, in the Czech Republic since 2007. It is a pity that its wider application is limited by the fear of its side effects; though it would be difficult to find a comparable risk of smoking with any drug. Papers describing this association were not methodologically correct and this relationship was also refused by the recent Cochrane Review publication - increased cardiovascular risk in connection with varenicline was not proved. Because the negative reports have been highly publicized, we consider to be useful to bring the overview, from which it is recognizable that varenicline is safe in terms of CV risks.
- Published
- 2014
217. Efficacy of interventions to combat tobacco addiction: Cochrane update of 2013 reviews
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Jamie, Hartmann-Boyce, Lindsay F, Stead, Kate, Cahill, and Tim, Lancaster
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Counseling ,Male ,Tobacco Use Disorder ,Benzazepines ,Tobacco Use Cessation Devices ,Pregnancy Complications ,Treatment Outcome ,Behavior Therapy ,Pregnancy ,Quinoxalines ,Antidepressive Agents, Second-Generation ,Humans ,Female ,Smoking Cessation ,Nicotinic Agonists ,Varenicline ,Bupropion ,School Health Services - Abstract
The Cochrane Collaboration is an international not-for profit organization which produces and disseminates systematic reviews. This paper is the second in a series of annual updates of Cochrane reviews on tobacco addiction interventions, covering new and updated reviews from 2013.In 2013, the Group published two new reviews and updated 11 others. This update summarizes and comments on these reviews as well as on a review of psychosocial interventions for smoking cessation in pregnant women, and presents pooled results from reviews of cessation interventions.New reviews in 2013 found: low-quality evidence that behavioural interventions with mood management components could significantly increase long-term quit rates in people with current [risk ratio (RR) = 1.47, 95% confidence interval (CI) = 1.13-1.92) and past (RR = 1.41, 95% CI = 1.13-1.77] depression; evidence from network meta-analysis that varenicline and combined forms of nicotine replacement therapy (NRT) are associated with higher quit rates than bupropion or single-form NRT (varenicline versus single-form NRT odds ratio (OR) = 1.57, 95% credibility interval (CredI) = 1.29-1.91; versus bupropion OR = 1.59, 95% CredI = 1.29-1.96); and no evidence of a significant increase in serious adverse events in trial participants randomized to varenicline or bupropion when compared to placebo controls. New evidence emerging from updated reviews suggests that counselling interventions can increase quit rates in pregnant women and that school-based smoking programmes with social competence curricula can lead to a significant reduction in uptake of smoking at more than a year. Updated reviews also suggested that naltrexone, selective serotonin re-uptake inhibitors and St John's wort do not have a significant effect on long-term smoking cessation.Cochrane systematic review evidence from 2013 suggests that adding mood management to behavioural support may improve cessation outcomes in smokers with current or past depression and strengthens evidence for previous conclusions, including the safety of varenicline and bupropion and the benefits of behavioural support for smoking cessation in pregnancy.
- Published
- 2014
218. [Determination of varenicline in the preparation Champix® with the use of two-dimensional capillary electrophoresis in connection with UV detection]
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Juraj, Piešťanský, Katarína, Maráková, Lucia, Veizerová, Jaroslav, Galba, and Peter, Mikuš
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Electrolytes ,Quinoxalines ,Electrophoresis, Capillary ,Benzazepines ,Varenicline - Abstract
This paper deals with an analytical method based on two dimensional capillary electrophoresis (CITP-CZE coupling) with simple UV-detection for the determination of a highly effective drug - varenicline. The method was elaborated with the possibility of its future connection with an advanced detection ending - mass spectrometry. The electrolytes for the CITP (LE = 10 mM NH4Ac + 5 mM HAc + 0,05% m-HEC; TE = 10 mM HAc) and CZE (BGE = 20 mM HAc) separation of varenicline were selected considering such requirements. The UV detector was set at the constant wavelength of 237 nm. The presented CITP-CZE-UV combination enabled rapid and effective evaluation of varenicline in the dosage forms with LOD 5.92 ng/ml.
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- 2014
219. In vivo and in vitro characterisation of a nonpeptide vasopressin V1A and V2 receptor antagonist (YM087) in the rat
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Louise M Burrell, Colin I. Johnston, John Risvanis, and Mareo Naitoh
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Male ,medicine.medical_specialty ,Vasopressin ,Systole ,Vasopressins ,medicine.drug_class ,Administration, Oral ,Urination ,Blood Pressure ,Biology ,Kidney ,Binding, Competitive ,Iodine Radioisotopes ,Rats, Sprague-Dawley ,Radioligand Assay ,Internal medicine ,Arginine vasopressin receptor 2 ,medicine ,Radioligand ,Animals ,Vasopressin receptor ,Pharmacology ,Arginine vasopressin receptor 1B ,Membranes ,Dose-Response Relationship, Drug ,Sodium ,Antagonist ,Benzazepines ,Receptor antagonist ,Rats ,Kinetics ,Endocrinology ,Liver ,Competitive antagonist ,Antidiuretic Hormone Receptor Antagonists ,hormones, hormone substitutes, and hormone antagonists - Abstract
This paper reports the in vitro and in vivo characterisation of a nonpeptide, orally active, vasopressin V(1A) and V(2) receptor antagonist, YM087 (methyl-1,4,5,6-tetrahydroimidazo[4, 5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride) in the rat. YM087 dose dependently displaced the vasopressin V(1A) receptor antagonist radioligand, 125I-labelled [d(CH(2))(5),sarcosine(7)]vasopressin at vasopressin V(1A) receptors in liver and kidney medulla membranes and caused a concentration dependent displacement of the vasopressin V(2) receptor antagonist radioligand [3H]desGly-NH(2)(9)[d(CH(2))(5), D-Ile(2), Ile(4)]vasopressin at vasopressin V(2) receptors in kidney medulla membranes. In vitro binding kinetic studies showed YM087 acted as a competitive antagonist at liver V(1A) and kidney V(1A) and V(2) vasopressin receptors. Oral administration of YM087 (0.1-3 mg/kg) dose dependently inhibited vasopressin binding to liver V(1A) and kidney V(1A) and V(2) vasopressin receptors over 24 h. Oral YM087 (1-3 mg/kg/day) for 7 days in normotensive rats caused a dose dependent aquaresis with no effect on systolic blood pressure. These results show that YM087 is an orally effective vasopressin V(1A) and V(2) receptor antagonist that may be useful in the treatment of conditions characterised by vasoconstriction and fluid retention such as congestive heart failure.
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- 1999
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220. Receptor systems participating in nicotine-specific effects
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István Sziráki, Audrey Hashim, Abel Lajtha, Myron Benuck, and Henry Sershen
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Male ,Nicotine ,medicine.medical_specialty ,Dopamine ,Microdialysis ,Nicotinic Antagonists ,Mecamylamine ,Nucleus accumbens ,Receptors, N-Methyl-D-Aspartate ,Nucleus Accumbens ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Dopamine receptor D1 ,Dopamine receptor D2 ,Internal medicine ,medicine ,Animals ,Chemistry ,Amphetamines ,Dopaminergic ,Cell Biology ,Benzazepines ,Rats ,Endocrinology ,Dopamine receptor ,Cholecystokinin B receptor ,Dopamine Antagonists ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists ,medicine.drug - Abstract
It is generally accepted that self-administration of drugs is prompted primarily by a reward system driven by an increase in extracellular dopamine in the nucleus accumbens. Recent findings that dopamine increase in the accumbens can be caused by many other factors, among them stress, suggest a more complex mechanism, and possibly differences in the reward system for different compounds. In the present paper we compare the effects of receptor-specific antagonists on the increase of dopamine induced by nicotine with that induced by cocaine in the nucleus accumbens in conscious rats. The compounds alone or together were injected intravenously, and dopamine level changes were measured via microdialysis. When administered together the effect of nicotine and cocaine on the level of dopamine in the accumbens was additive. Apparently there is some interaction between the two compounds, since nicotine had no effect after combined nicotine and cocaine administration. Perhaps the available dopamine pool was exhausted by the prior administration. The nicotinic antagonist mecamylamine, the muscarinic antagonist atropine, and the NMDA glutamate receptor antagonist MK-801 each blocked nicotine-induced dopamine release in the accumbens, indicating the participation of more than a single receptor system in the nicotine-induced effect. These three antagonists did not inhibit cocaine-induced dopamine increase in the accumbens, indicating the lack of a role of these receptors in the cocaine effect under our experimental conditions. SCH-23390, a dopamine D1 receptor antagonist, blocked both nicotine- and cocaine-induced effects, indicating the possible role of this receptor in these reward effects. The results indicate that there are differences in some of the receptors mediating the central effects of the two compounds examined, nicotine and cocaine, although each influences dopamine levels, and that the two compounds interact.
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- 1998
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221. The behavioural effects of pramipexole, a novel dopamine receptor agonist
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Jerzy Maj, Zofia Rogóż, Krzysztof Kołodziejczyk, and Grazyna Skuza
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Male ,Agonist ,Fluphenazine ,Dyskinesia, Drug-Induced ,Spiperone ,medicine.medical_specialty ,medicine.drug_class ,Injections, Subcutaneous ,Dopamine Agents ,Motor Activity ,Pharmacology ,Body Temperature ,Antiparkinson Agents ,Levodopa ,Mice ,Pramipexole ,Dopamine receptor D3 ,Dopamine receptor D2 ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Benzothiazoles ,Rats, Wistar ,Clozapine ,Catalepsy ,Dose-Response Relationship, Drug ,Receptors, Dopamine D2 ,Chemistry ,Receptors, Dopamine D3 ,Benzazepines ,Rats ,Thiazoles ,Endocrinology ,Dopamine receptor ,Dopamine Agonists ,Dopamine Antagonists ,Haloperidol ,Stereotyped Behavior ,Sulpiride ,medicine.drug - Abstract
Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.
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- 1997
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222. Effectiveness of a Multi-Component Smoking Cessation Support Programme (McSCSP) for Patients with Severe Mental Disorders: Study Design
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Julio Bobes, Eva M. Díaz-Mesa, Fernando Sarramea, María Paz García-Portilla, Gonzalo Galván, Leticia García-Álvarez, Josefa Garcia-Blanco, Edorta Elizagarate, and Pilar A. Saiz
- Subjects
Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Motivational interviewing ,Psychological intervention ,lcsh:Medicine ,Severity of Illness Index ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Medicine ,Nicotinic Agonists ,Varenicline ,PUBLIC, ENVIRONMENTAL AND OCCUPATIONAL HEALTH ,bipolar disorder ,Clinical Trials as Topic ,Smoking ,Tobacco Use Cessation Devices ,varenicline ,Motivational therapy ,controlled-trial ,schizophrenia ,transdermal nicotine patches ,bupropion ,Psychotherapy, Group ,Antidepressive Agents, Second-Generation ,Schizophrenic Psychology ,rating-scale ,Psychopathology ,medicine.medical_specialty ,substance use ,Motivational Interviewing ,tobacco use ,fagerstrom test ,Article ,Quinoxalines ,Humans ,Bipolar disorder ,Psychiatry ,nicotine dependence ,business.industry ,cigarette-smoking ,lcsh:R ,Public Health, Environmental and Occupational Health ,psychotic disorder ,Benzazepines ,medicine.disease ,chemistry ,Smoking cessation ,Smoking Cessation ,HEALTH, TOXICOLOGY AND MUTAGENESIS ,business ,physical health ,Follow-Up Studies - Abstract
Only a few studies have examined the efficacy and safety of smoking cessation programmes in patients with mental disorders. The aim of this paper is to describe in detail the methodology used in the study as well as the Multi-component Smoking Cessation Support Programme in terms of pharmacological treatments and psychological interventions. An open-label 9-month follow-up study was conducted in Spain. A total of 82 clinically stable outpatients with schizophrenia, schizoaffective or bipolar disorder were enrolled. Treatment consisted of a programme specifically developed by the research team for individuals with severe mental disorders. The programme consisted of two phases: (1) weekly individual motivational therapy for 4-12 weeks, and (2) a 12-week active treatment phase. During this phase, at each study visit patients received a one- or two-week supply of medication (transdermal nicotine patches, varenicline or bupropion) with instructions on how to take it, in addition to group psychotherapy for smoking cessation. Evaluations were performed: (1) at the time of enrolment in the study, (2) during the 12-week active treatment phase of the study (weekly for the first 4 weeks and then biweekly), and (3) after the end of this phase (two follow-up assessments at weeks 12 and 24). Evaluations included: (1) smoking history, (2) substance use, (3) psychopathology, (4) adverse events, and (5) laboratory tests. The importance of this study lies in addressing a topical issue often ignored by psychiatrists: the unacceptably high rates of tobacco use in patients with severe mental disorders. This study was conducted without financial support from any pharmaceutical company. It was partly supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (FIS PI10/01758), and CIBERSAM. We thank Sharon Grevet for her English assistance. She was sponsored by research grants
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- 2013
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223. A systematic review of studies assessing the association between adherence to smoking cessation medication and treatment success
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Tobias, Raupach, Jamie, Brown, Aleksandra, Herbec, Leonie, Brose, and Robert, West
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Treatment Outcome ,Dopamine Uptake Inhibitors ,Quinoxalines ,Smoking ,Humans ,Smoking Cessation ,Nicotinic Agonists ,Benzazepines ,Varenicline ,Bupropion ,Medication Adherence - Abstract
Lack of adherence to smoking cessation medication regimens is assumed to play a significant role in limiting their effectiveness. This study aimed to assess evidence for this assumption.A systematic search was conducted, supplemented by expert consultation, of papers reporting on randomized trials and observational studies examining the association between adherence to cessation medication and the success of quit attempts. To rule out reverse causality, only studies where adherence was assessed prior to relapse were included. Five studies met the inclusion criteria and results were extracted independently by two researchers. Heterogeneity between studies precluded a pooled analysis of the data.Studies varied widely with regard to both the definition of adherence and outcome measures. The included studies only addressed adherence to nicotine replacement therapy. One study of lozenge use found that the amount of medication used between 1 and 2 weeks after the quit date predicted abstinence at 6 weeks [adjusted odds ratio (OR) for 'high' versus 'low' lozenge use 1.25; 95% confidence interval (CI) = 1.05-1.50; P 0.02]. Similarly, one study found a significant impact of oral nicotine consumption during the first week on abstinence at 4 weeks (adjusted OR per additional mg/day = 1.05; CI = 1.01-1.10). Another study found that participants using nicotine replacement therapy for at least 5 weeks were significantly more likely to self-report continuous abstinence at 6 months. The remaining two studies failed to find a significant effect of treatment duration on outcome at 1 and 2 years but had very low power to detect such an effect.There is modest evidence to support the assumption that lack of adherence to nicotine replacement therapy regimens undermines effectiveness in clinical studies.
- Published
- 2013
224. Lorcaserin: a novel serotonin 2C agonist for the treatment of obesity
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William L. Baker, Darren Luon, and Stefanie C. Nigro
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Topiramate ,medicine.medical_specialty ,business.industry ,Body Weight ,General Medicine ,Pharmacology ,Diethylpropion ,Benzazepines ,Lorcaserin ,Orlistat ,Eating ,Pharmacotherapy ,Phentermine ,Adjunctive treatment ,Lipase inhibitors ,Weight Loss ,medicine ,Receptor, Serotonin, 5-HT2C ,Humans ,Anti-Obesity Agents ,Obesity ,Intensive care medicine ,business ,Serotonin 5-HT2 Receptor Agonists ,medicine.drug - Abstract
Obesity has become an epidemic in the United States and its prevalence continues to increase. Adjunctive treatment with pharmacotherapy is often reserved for individuals who fail to achieve their intended weight goals with diet and exercise alone. Current approved therapies for weight loss include phentermine, diethylpropion, orlistat, and phentermine/topiramate. The objective of this paper was to review the place of lorcaserin, a novel serotonin 2C agonist, which was FDA approved in July 2012. Unlike contemporary lipase inhibitors and sympathomimetic amines, lorcaserin is purported to reduce food consumption and increase satiety.A systematic review of the literature for all relevant articles was performed through January 2013 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts using key words related to lorcaserin.Three phase III clinical studies have been published evaluating the efficacy and safety of lorcaserin in various obese populations. A higher proportion of patients receiving lorcaserin (∼47%) lost more than 5% body weight from baseline in comparison with the placebo group (∼25%; p 0.05 in all studies). Those receiving the recommended dose of lorcaserin 10 mg twice daily lost on average ∼6 kg of body weight from baseline versus ∼3 kg with placebo. Patients with diabetes mellitus also saw significant reductions in their HbA1c with lorcaserin (∼0.9%) versus placebo (∼0.4%; p 0.001). Lorcaserin is generally well tolerated with the most commonly experienced adverse events being nausea, dizziness, headache, upper respiratory tract infections, and nasopharyngitis. Cardiovascular evaluations showed no appreciable increase in valvulopathy with lorcaserin use versus placebo.For now, pharmacists should continue to recommend the use of lorcaserin as a complement to, not in lieu of, ongoing lifestyle and behavioral modification.
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- 2013
225. How confidence intervals become confusion intervals
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Ben Vandermeer, G M Allan, and James McCormack
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Risk ,Epidemiology ,Debate ,Confidence intervals ,Health Informatics ,law.invention ,New medications ,Randomized controlled trial ,law ,Statistical significance ,Quinoxalines ,Statistics ,medicine ,Humans ,Point estimation ,Confusion ,Randomized Controlled Trials as Topic ,Evidence-Based Medicine ,business.industry ,Uncertainty ,Anticoagulants ,Evidence-based medicine ,Benzazepines ,Confidence interval ,Potential harm ,Treatment Outcome ,Statistical analysis ,Cardiovascular Diseases ,Data Interpretation, Statistical ,Evidence based medicine ,medicine.symptom ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Varenicline ,business ,Cognitive psychology - Abstract
Background Controversies are common in medicine. Some arise when the conclusions of research publications directly contradict each other, creating uncertainty for frontline clinicians. Discussion In this paper, we review how researchers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear understanding of confidence intervals. The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings. We describe three examples of controversy around the potential benefit of a medication, a comparison between new medications, and a medication with a potential harm. The examples include the highest levels of evidence, both meta-analyses and randomized controlled trials. We will show how in each case the confidence intervals and point estimates were very similar. The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance. Summary These opposing conclusions are false disagreements that create unnecessary clinical uncertainty. We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results.
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- 2013
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226. [The rare case of Bland-White-Garland syndrome in adult patient]
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Iu M, Alekseeva, V I, Potievskaia, E A, Sakovich, A V, Sitnikov, E L, Soiustova, V A, Fin'ko, and A V, Ardashev
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Adult ,Heart Failure ,Cardiovascular Surgical Procedures ,Coronary Vessel Anomalies ,Mitral Valve Insufficiency ,Cardiovascular Agents ,Syndrome ,Benzazepines ,Pulmonary Artery ,Coronary Angiography ,Prognosis ,Coronary Vessels ,Treatment Outcome ,Multidetector Computed Tomography ,Humans ,Female ,Ivabradine ,Metoprolol - Abstract
We present analysis of a case history of a patient with rare congenital heart disorder - Bland-White-Garland syndrome. The 25 years old women was first diagnosed with this disorder during an examination in the cardiological department of the Moscow clinical hospital No83. The paper contains discussion of difficulties of diagnosis and peculiarities of management of adults with this pathology as well as of a problem of the choice of further therapeutic approaches.
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- 2012
227. Use of the Patient Health Questionnaire-2 to predict suicidal ideations in patients taking varenicline
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Christopher M, Cowan, Jennifer S, Wink, and Kent J, DeZee
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Adult ,Male ,Depression ,Smoking ,Smoking Prevention ,Benzazepines ,Middle Aged ,Suicidal Ideation ,Risk Factors ,Quinoxalines ,Surveys and Questionnaires ,Humans ,Female ,Smoking Cessation ,Nicotinic Agonists ,Varenicline - Abstract
Varenicline, when taken for smoking cessation, has been associated with suicidal ideations (SI), but the incidence and risk factors for SI are largely unknown. The aim of this paper was to describe the incidence and pretreatment patient factors that are associated with SI when taking varenicline. We conducted a smoking cessation trial of 217 patients at a single center, all of whom took varenicline. Between 6 and 18 months after study completion (when the risk for SI became known), we successfully contacted 72 (response rate 33%) and queried them for SI during varenicline treatment. Of these, 4 (6%) had SI. Self-reported history of depression was not associated with SI (p = 0.11), but depressive symptoms at the time of varenicline initiation as measured by the Patient Health Questionnaire-8 (p = 0.004) and Patient Health Questionnaire-2 (p = 0.007) were associated with SI. The Patient Health Questionnaire-2 (which is only two questions) had a sensitivity of 75% and a specificity of 90% to predict SI. We conclude that current depressive symptoms, not necessarily a history of depression, are associated with SI when taking varenicline for smoking cessation. Providers should consider screening for depressive symptoms before treatment with varenicline. (Am J Addict 2012;00:1-7).
- Published
- 2012
228. Very low rate and light smokers: smoking patterns and cessation-related behaviour in England, 2006-11
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Daniel, Kotz, Jennifer, Fidler, and Robert, West
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Adult ,Counseling ,Male ,Motivation ,Health Behavior ,Smoking ,Tobacco Use Disorder ,Benzazepines ,Cross-Sectional Studies ,Treatment Outcome ,Dopamine Uptake Inhibitors ,England ,Quinoxalines ,Humans ,Female ,Smoking Cessation ,Longitudinal Studies ,Nicotinic Agonists ,Varenicline ,Bupropion - Abstract
There is a growing interest in very low rate [fewer than one cigarette per day (CPD)] and light (one to nine CPD) smokers and in some parts of the world their numbers appear to be increasing. This paper examined changes in prevalence over the past 5 years, cessation patterns, and smoking and demographic characteristics of very low rate, light and moderate-to-heavy (10+ CPD) smokers in England.Cross-sectional and longitudinal data from aggregated monthly waves of a household survey: the Smoking Toolkit Study.England.A total of 23,245 smokers interviewed between November 2006 and May 2011 and 4147 who provided data at 6-month follow-up.We compared the demographic and smoking characteristics between the three groups of smokers at baseline, and the rate of attempts to quit, use of aids to cessation and success of quit attempts at follow-up.Very low rate smoking remained extremely rare (1.9% of smokers in 2006 to 2.8% in 2011), but light smoking became increasingly common (23.9-32.8%). Compared with moderate-to-heavy smokers, very low rate and light smokers were younger, more often female and from a higher socio-economic background. They were more motivated to quit and enjoyed smoking less. During the 6-month follow-up period, light smokers, but not very low rate smokers, were more likely to attempt to quit than moderate-to-heavy smokers. When they tried to quit, very low rate and light smokers used aids to cessation less than moderate-to-heavy smokers but still used them to a substantial degree: 18%, 31% and 44% used over-the-counter nicotine replacement therapy in their most recent quit attempt for the three types of smoker, respectively. Even very low rate smokers had a substantial failure rate: 65% failed in their most recent quit attempt within 6 months.Very low rate (fewer than one cigarette per day) and light (one to nine cigarettes per day) smokers in England are at least as motivated to quit as heavier smokers. Although they use cessation medication less than heavier smokers and are more likely to succeed, they still use such medication and fail in quit attempts to a substantial degree.
- Published
- 2011
229. Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects
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Susan E, Shoaf, Patricia, Bricmont, and Suresh, Mallikaarjun
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Adult ,Male ,Adolescent ,Dose-Response Relationship, Drug ,Pharmacokinetic Dynamic Relationships ,Urination ,Benzazepines ,Middle Aged ,Young Adult ,Ketoconazole ,Double-Blind Method ,14-alpha Demethylase Inhibitors ,Area Under Curve ,Tolvaptan ,Cytochrome P-450 CYP3A ,Cytochrome P-450 CYP3A Inhibitors ,Humans ,Drug Interactions ,Female ,Enzyme Inhibitors ,Rifampin ,Antidiuretic Hormone Receptor Antagonists - Abstract
Before these trials were done, the effects of CYP3A4 inhibition and induction on the pharmacokinetics (PK) and pharmacodynamics (PD) of tolvaptan in healthy subjects were unknown. As tolvaptan is a CYP3A4 substrate, knowing the effects of inhibition and induction on CYP3A4-mediated metabolism was important for dosing recommendations.This paper describes the changes in tolvaptan PK and PD following inhibition or induction of CYP3A4 and explores the mechanisms behind the disparity seen between tolvaptan PK and effects on urine output. It also discusses the concentrations at which tolvaptan produces its maximal response on urine output and the timing of the onset and offset of this response. AIMS In vitro studies indicated CYP3A4 alone was responsible for tolvaptan metabolism. To determine the effect of a CYP3A4 inhibitor (ketoconazole) and a CYP3A4 inducer (rifampicin) on tolvaptan pharmacokinetics (PK) and pharmacodynamics (PD), two clinical trials were performed.For CYP3A4 inhibition, a double-blind, randomized (5:1), placebo-controlled trial was conducted in 24 healthy subjects given either a single 30 mg dose of tolvaptan (n= 19) or matching placebo (n= 5) on day 1 with a 72 h washout followed by a 3 day regimen of 200 mg ketoconazole, once daily with 30 mg tolvaptan or placebo also given on day 5. For CYP3A4 induction, 14 healthy subjects were given a single dose of 240 mg tolvaptan with 48 h washout followed by a 7 day regimen of 600 mg rifampicin, once daily, with 240 mg tolvaptan also given on the seventh day.When co-administered with ketoconazole, mean C(max) and AUC(0,∞) of tolvaptan were increased 3.48- and 5.40-fold, respectively. Twenty-four hour urine volume increased from 5.9 to 7.7 l. Erythromycin breath testing showed no difference following a single dose of tolvaptan. With rifampicin, tolvaptan mean C(max) and AUC were reduced to 0.13- and 0.17-fold of tolvaptan administered alone. Twenty-four hour urine volume decreased from 12.3 to 8.8 l.Tolvaptan is a sensitive CYP3A4 substrate with no inhibitory activity. Due to the saturable nature of tolvaptan's effect on urine excretion rate, changes in the pharmacokinetic profile of tolvaptan do not produce proportional changes in urine output.
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- 2011
230. Tolvaptan for the treatment of heart failure: a review of the literature
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Steven R. Goldsmith, Andrew P. Ambrosy, and Mihai Gheorghiade
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Vasopressin ,medicine.medical_specialty ,Consensus ,Tolvaptan ,Urine sodium ,Thirst ,Internal medicine ,Toxicity Tests ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,Intensive care medicine ,Diuretics ,Pharmacology ,Heart Failure ,Clinical Trials as Topic ,business.industry ,General Medicine ,Benzazepines ,medicine.disease ,Diuresis ,Clinical trial ,Free water clearance ,Disease Models, Animal ,Treatment Outcome ,Heart failure ,Ambulatory ,Cardiology ,medicine.symptom ,business ,medicine.drug ,Hyponatremia - Abstract
It has been25 years since it was first discovered that arginine vasopressin levels are elevated in heart failure and this elevation is proportional to the severity of heart failure. Tolvaptan is an oral nonpeptide V₂-selective antagonist and has been shown to induce free water excretion without increasing urine sodium, an effect termed 'aquaresis'.This paper aims to review the physiology, chemistry, pharmacokinetics, clinical efficacy and safety of tolvaptan in HF. A PubMed literature search was performed using 'tolvaptan' and the MeSH term 'heart failure', yielding 89 references.Clinical trials conducted in ambulatory and hospitalized patients with HF have found treatment with tolvaptan causes rapid and sustained body weight reductions concurrent with increases in urine output, improves and/or normalizes serum sodium in hyponatremic patients, reduces signs and symptoms of congestion and increases thirst. However, tolvaptan has not been shown to decrease HF re-hospitalization or mortality. As an adjunct to standard therapy, tolvaptan is unique in that it is virtually the only novel agent tested in patients hospitalized for acute heart failure syndrome (AHFS) to reach its primary end point for short-term efficacy without causing deleterious side effects. There is theoretical concern that chronic V₂ receptor blockade may cause harmful long-term side effects via enhanced V(1a) receptor activation, potentially offsetting any favorable effects on congestion and hyponatremia. The 'vaptan' class of drugs is an active and promising area for clinical investigation and future research is necessary to clarify the therapeutic role of selective and nonselective vasopressin inhibition in chronic HF and AHFS.
- Published
- 2011
231. ChemInform Abstract: Orally Active, Nonpeptide Vasopressin V2 Receptor Antagonists: A Novel Series of 1-(4-(Benzoylamino)benzoyl)-2,3,4,5-tetrahydro-1H- benzazepines and Related Compounds
- Author
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Michinori Tanaka, Youichi Yabuuchi, Kazuyoshi Kitano, Keizo Kan, Hisashi Miyamoto, Yoshitaka Yamamura, Hiroshi Yamashita, K. Kondo, Michiaki Tominaga, Toyoki Mori, Hidenori Ogawa, Kenji Nakaya, and Shigeki Nakamura
- Subjects
Ortho position ,Benzazepines ,chemistry.chemical_compound ,Orally active ,Chemistry ,Stereochemistry ,Aquaretic ,Arginine vasopressin receptor 2 ,General Medicine ,Ring (chemistry) ,Receptor ,Benzazepine - Abstract
This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.
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- 2010
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232. [Ivabradine in coronary heart disease: experimental and clinical pharmacology]
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Atul, Pathak, Alain, Berdeaux, Paul, Mulder, and Christian, Thuillez
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Heart Failure ,Ventricular Dysfunction, Left ,Heart Rate ,Animals ,Humans ,Cardiovascular Agents ,Coronary Disease ,Ivabradine ,Benzazepines - Abstract
The present paper reviews clinical evidence underlining the role of ivabradine in the management of patient with ischemic heart disease. Reduction in heart rate mediated by this selective I(f) current inhibitor has been associated with anti-ischemic efficacy without any effect on haemodynamic or myocardial contractility. The antianginal efficacy of ivabradine is similar or superior to that of conventional anti-ischemic agents. Moreover combination therapy with ivabradine provides substantial benefit in patients already receiving beta-blocker. Prognostic efficacy of ivabradine is evaluated in a large program of studies, among which BEAUTIFUL in coronary patients with left ventricular dysfunction. The SIGNIFY study is ongoing in stable coronary patients without ventricular dysfunction. Furthermore the SHIFT trial will evaluate ivabradine benefits in heart failure patients, whatever the origin, ischemic or not.
- Published
- 2010
233. Improving the effectiveness of tobacco use cessation (TUC)
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Ian G, Needleman, Vivian I, Binnie, Anja, Ainamo, Alan B, Carr, Angela, Fundak, Anne, Koerber, Anne, Koeber, Kerstin, Ohrn, and Josine, Rosseel
- Subjects
Counseling ,Tobacco Use Cessation ,Nicotine ,Smoking ,Benzazepines ,Chewing Gum ,Behavior Therapy ,Quinoxalines ,Dental Offices ,Antidepressive Agents, Second-Generation ,Humans ,Nicotinic Agonists ,Varenicline ,Bupropion ,Referral and Consultation - Abstract
This paper includes an update of a Cochrane systematic review on tobacco use cessation (TUC) in dental settings as well as narrative reviews of possible approaches to TUC and a more detailed discussion of referral for specialist TUC services. On the basis of these reviews we conclude that interventions for tobacco users in the dental setting increase the odds of quitting tobacco. However, the evidence is derived largely from patients using smokeless tobacco. Pharmacotherapy (such as nicotine replacements, bupropion and varenicline) is recommended for TUC in medical settings but has received little assessment in dental applications, although such evidence to date is promising. Whether the dental setting or referral to specialist TUC services is the most effective strategy to help people to quit tobacco use is unclear. An effective specialist service providing best available TUC care alone may not be the answer. Clearly, such services should be both accessible and convenient for tobacco users. Closer integration of specialist services with referrers would also be advantageous in order to guide and support oral health professionals make their referral and to maximise follow-up of referred tobacco users. Future research direction may consider investigating the most effective components of TUC in the dental settings and community-based trials should be a priority. Pharmacotherapy, particularly nicotine replacement therapy, should be more widely examined in dental settings. We also recommend that various models of referral to external and competent in-house TUC specialist services should be examined with both experimental and qualitative approaches. In addition to overall success of TUC, important research questions include facilitators and barriers to TUC in dental settings, preferences for specialist referral, and experiences of tobacco users attempting to quit, with dental professionals or specialist services, respectively.
- Published
- 2010
234. Differential effects of methamphetamine and SCH23390 on the expression of members of IEG families of transcription factors in the rat striatum
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Genevieve Beauvais, Bruce Ladenheim, Michael T. McCoy, Jean Lud Cadet, and Subramaniam Jayanthi
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Male ,CAMP-Responsive Element Modulator ,medicine.medical_specialty ,JUNB ,Nerve Tissue Proteins ,Fos-Related Antigen-2 ,Biology ,Article ,Methamphetamine ,Cyclic AMP Response Element Modulator ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Dopamine receptor D1 ,Internal medicine ,Gene expression ,medicine ,Animals ,RNA, Messenger ,Phosphorylation ,education ,Molecular Biology ,Genes, Immediate-Early ,education.field_of_study ,General Neuroscience ,Receptors, Dopamine D1 ,JNK Mitogen-Activated Protein Kinases ,Meth ,Benzazepines ,Corpus Striatum ,Rats ,Cytoskeletal Proteins ,Endocrinology ,chemistry ,Early Growth Response Transcription Factors ,Dopamine Antagonists ,Central Nervous System Stimulants ,Neurology (clinical) ,Immediate early gene ,Proto-Oncogene Proteins c-fos ,Developmental Biology ,medicine.drug ,FOSB - Abstract
Methamphetamine (METH) is a psychostimulant that can cause long-lasting neurodegenerative effects in humans and animals. These toxic effects appear to occur, in part, via activation of dopamine (DA) D1 receptors. This paper assessed the possibility that the DA D1 receptor antagonist, SCH23390, might inhibit METH-induced changes in the expression of several members of immediate early genes (IEGs) which are known to control more delayed expression of other genes. We found that injections of METH (4×10 mg/kg, given at 2 hr intervals) caused significant increases in c-fos and fra-2 expression which lasted from 30 min to 4 hr. Pre-treatment with SCH23390, given 30 min before each METH injection, completely blocked METH-induced expression of c-fos, but only partially inhibited fra-2 mRNA expression. These results were confirmed by western blot analysis which showed METH-induced changes in c-Fos protein expression that were blocked by pretreatment with SCH23390. There were also delayed METH-induced DA D1 receptor-dependent effects on fosB mRNA expression. Even though fra-1 expression was not affected by pretreatment with METH alone, the repeated injections of SCH23390 caused substantial decreases in fra-1 mRNA expression in both the presence and absence of METH. The repeated injections of METH caused no changes in the mRNAs for c-jun, junB or junD. However, there were significant increases in the phosphorylation of c-Jun protein (ser63). Phosphorylation of c-Jun occurred in a delayed fashion (16 and 24 hours after the last METH injections) and was attenuated by SCH23390 pretreatment. Interestingly, SCH23390 given alone caused significant decreases in phospho-c-Jun at all time-points. The METH injections also caused delayed induction in the expression of members of the Egr family of transcription factors in a DA D1 receptor-dependent fashion. Repeated injections of SCH23390 caused substantial suppression of basal striatal egr-1 and egr-2 mRNA expression but not of that of egr-3. Both crem and arc mRNA levels were induced by METH in a SCH23390-sensitive fashion. Moreover, multiple injections of SCH23390 given alone caused marked inhibition of basal arc expression. These results show that multiple injections of METH can differentially affect the expression of several IEGs, some of which occurred in a DA D1 receptor dependent fashion. The SCH23390-mediated suppression of basal fra-1, egr-1, and egr-2 mRNA levels suggests that their basal expression in the striatum might be dependent on tonic stimulation of the DA D1 receptor.
- Published
- 2010
235. Dopamine D1 and opioid receptor binding changes in the limbic system of sleep deprived rats
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Paola Fadda, G.L. Gessa, M C Martellotta, Walter Fratta, and M.G. De Montis
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Male ,medicine.medical_specialty ,medicine.drug_class ,(+)-Naloxone ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Limbic system ,Mesencephalon ,Internal medicine ,Opioid Receptor Binding ,Limbic System ,medicine ,Animals ,SCH-23390 ,Receptors, Dopamine D1 ,Enkephalins ,Cell Biology ,Benzazepines ,Enkephalin, Ala(2)-MePhe(4)-Gly(5) ,Enkephalin, Leucine-2-Alanine ,Corpus Striatum ,Rats ,Sleep deprivation ,Endocrinology ,medicine.anatomical_structure ,Opioid ,chemistry ,Receptors, Opioid ,Sleep Deprivation ,medicine.symptom ,Psychology ,Cyclase activity ,Opioid antagonist ,medicine.drug - Abstract
Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was potently antagonized by the administration of the D 1 selective antagonist SCH 23390 and by the opioid antagonist naloxone. In this paper we show that concomitantly to this behavior, an increased number of D 1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain area. These data suggest an active role of limbic dopamine and opioid systems in the generation of arousal and insomnia related to sleep deprivation-induced stress.
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- 1992
- Full Text
- View/download PDF
236. Varenicline in the management of smoking cessation: a single technology appraisal
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D, Hind, P, Tappenden, J, Peters, and K, Kenjegalieva
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Clinical Trials as Topic ,Cost-Benefit Analysis ,Quinoxalines ,Antidepressive Agents, Second-Generation ,Humans ,Smoking Cessation ,Nicotinic Agonists ,Quality-Adjusted Life Years ,Benzazepines ,Varenicline ,Bupropion - Abstract
This paper presents a summary of the submission's evidence for the clinical effectiveness and cost-effectiveness of varenicline for smoking cessation included four studies of varenicline (one of which was commercial-in-confidence) and a meta-analysis of varenicline versus nicotine replacement therapy (NRT), bupropion and placebo. Two controlled trials of 12 weeks of varenicline versus sustained-release bupropion and placebo suggested that varenicline results in a statistically significant improvement in the odds of quitting at 12 weeks [odds ratio (OR) for quit rate during last 4 weeks of the study: 1.90-1.93 (p0.001) varenicline versus bupropion; 3.85 (p0.001) varenicline versus placebo). The ORs for sustained abstinence (weeks 9-52) for varenicline versus bupropion were 1.77 (p = 0.004) and 1.46 (p = 0.057), and for varenicline versus placebo were 2.66-3.09 (p0.01). A placebo-controlled maintenance trial examined whether a further 12 weeks of varenicline would maintain the rate of abstinence among those successfully treated on one 12-week course [OR = 2.48 at week 24 for varenicline versus placebo (p0.001)]. The meta-analysis suggested that varenicline was superior to placebo and bupropion at 1 year and 3 months. Based on indirect comparisons, varenicline was reported to be superior to NRT when compared with placebo or all controls at 1 year and 3 months. The submission presented a state transition model to estimate the incremental cost-effectiveness of varenicline compared with bupropion, NRT and placebo. The model suggests that varenicline dominates bupropion, NRT and placebo.Treatment efficacy was based on a pooled analysis of 1-year quit rates from the varenicline clinical trials. Assuming a willingness-to-pay threshold range of 20,000-30,000 pounds per quality-adjusted life-year gained, the probabilistic sensitivity analysis suggests that the probability that varenicline produces the greatest amount of net benefit is 0.70. Weaknesses of the manufacturer's submission include the assumption that only a single quit attempt using a single smoking cessation intervention is made, the presence of multiple computational errors and a limited sensitivity analysis. In conclusion, varenicline is likely to be clinically and cost-effective for smoking cessation assuming that each user makes a single quit attempt. The key area of uncertainty concerns the long-term experience of subjects who have remained abstinent from smoking beyond 12 months. The guidance issued by the National Institute for Health and Clinical Excellence in July 2007 states that varenicline is recommended within its licensed indications as an option for smokers who have expressed a desire to quit smoking and that varenicline should normally be prescribed only as part of a programme of behavioral support.
- Published
- 2009
237. Multimodal techniques for smoking cessation: a review of their efficacy and utilisation and clinical practice guidelines
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V I, Reus and B J, Smith
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Complementary Therapies ,Nicotine ,Smoking Prevention ,Tobacco Use Disorder ,Benzazepines ,Combined Modality Therapy ,Psychotherapy ,Treatment Outcome ,Quinoxalines ,Practice Guidelines as Topic ,Humans ,Drug Therapy, Combination ,Smoking Cessation ,Nicotinic Agonists ,Varenicline - Abstract
Nicotine addiction is a complex, chronic condition with physiological and psychological/behavioural aspects that make smoking cessation extremely difficult. This paper reviews current recommendations for smoking cessation and the efficacy of pharmacotherapy and behavioural modification techniques, used either alone or in combination, for smoking cessation.Abstinence rates for pharmacotherapies range from approximately 16% to approximately 30% at 1-year follow-up, with efficacy odds ratios (ORs) compared with placebo of approximately 1.7 for nicotine replacement therapy (NRT), approximately 1.9 for bupropion sustained release and approximately 3.0 for varenicline. Behaviour modification therapies have achieved quit rates of between 8% and 43% for up to 1 year, with ORs in comparison to no treatment of between approximately 1.2 and approximately 2.2. No direct comparisons have been made between pharmacotherapy alone and psychological behaviour strategies alone. However, combining physiological approaches with counselling significantly increases the odds of quitting compared with either technique alone.Applying multimodal techniques for the treatment of nicotine addiction is the recommended approach and has demonstrated the potential to improve rates of permanent abstinence in smokers attempting cessation. While the numbers of patients receiving help and advice regarding smoking cessation is increasing, the multimodal approach appears to be currently underutilised by clinicians and therefore smoking cessation strategies are not being optimised.
- Published
- 2008
238. Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system
- Author
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Walter Fratta, Paola Fadda, M.G. Demontis, Paola Devoto, and M C Martellotta
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Male ,medicine.medical_specialty ,Dopamine ,Receptors, Dopamine ,chemistry.chemical_compound ,Dopamine receptor D1 ,Limbic system ,Reference Values ,Internal medicine ,Limbic System ,medicine ,Animals ,Neurotransmitter ,SCH-23390 ,Receptors, Dopamine D1 ,General Neuroscience ,Antagonist ,Rats, Inbred Strains ,Benzazepines ,Corpus Striatum ,Rats ,Kinetics ,Sleep deprivation ,medicine.anatomical_structure ,Endocrinology ,chemistry ,D1 receptor ,Dopamine-stimulated adenylate cyclase ,Rat ,Stress ,Sleep Deprivation ,medicine.symptom ,Psychology ,Cyclase activity ,Adenylyl Cyclases ,medicine.drug - Abstract
Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rats displayed particular behaviour characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behaviour was potently antagonized by the administration of the D1-selective antagonist SCH 23390. In this paper we show that concomitantly to this behaviour, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. These data suggest an active role of limbic D1 receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.
- Published
- 1990
- Full Text
- View/download PDF
239. Recognition and treatment of hyponatremia in acutely ill hospitalized patients
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Robert A. Balk and Gourang P. Patel
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Nephrology ,medicine.medical_specialty ,Vasopressin ,Critical Illness ,Tolvaptan ,law.invention ,law ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Pyrroles ,Intensive care medicine ,Randomized Controlled Trials as Topic ,Pharmacology ,Inpatients ,business.industry ,nutritional and metabolic diseases ,Azepines ,Benzazepines ,medicine.disease ,Intensive care unit ,Lixivaptan ,Clinical trial ,Arginine Vasopressin ,Benzamides ,Practice Guidelines as Topic ,Conivaptan ,Hyponatremia ,business ,Antidiuretic Hormone Receptor Antagonists ,medicine.drug - Abstract
Objective: The objective of this paper was to discussthe diagnosis, pathophysiology, and management of hyponatremia among critically ill, hospitalized patients (eg, after surgery or in the intensive care unit). Methods: English-language literature published between 1967 and 2006 was searched using several key words ( AVP receptor antagonists, hyponatremia, SIADH, conivaptan, tolvaptan, and lixivaptan ) and by accessing MEDLINE and ScienceDirect. Meeting abstracts from scientific sessions (American Society of Nephrology Renal Week 2004 and the Endocrine Society's 87th Annual Meeting [2005]) were reviewed. The package insert for conivaptan hydrochloride injection was referenced from . Clinical trials included in this review were randomized and placebo controlled. Results: Based on the literature we researched, hyponatremia is the most common electrolyte disorder encountered in critical care and is associated with a variety of conditions, including congestive heart failure and the syndrome of inappropriate antidiuretic hormone secreion. Because hyponatremia can arise in hypervolemic, euvolernic, and hypovolemic states, clinicians may not recognize its presence and cause. Incorrect rnanagement can lead to significant morbidity and mortality. Physicians need to recognize risk factors and symptoms and use appropriate treatment guidelines for hyponatremia. Traditionally, therapy for hyponatremia has been limited by efficacy and safety concerns. Arginine vasopressin (AVP) receptor antagonists, therapeutic agents that promote aquaresis in patients with hyponatremia by targeting V 1a receptors in the vascular smooth muscle, V 2 receptors in the kidney, or both, are under development. A dual-receptor antagonist targeting both V 1a and V 2 receptors is now approved for the treatment of euvolernic hyponatremia in hospitalized patients. Conclusions: Hyponatremia, an electrolyte abnormalityfound in critically ill patients, can be associated with significant morbidity and mortality. AVP receptor antagonists show promise as effective and tolerable treatments for patients with hyponatremia.
- Published
- 2007
240. Study into a possible mechanism responsible for the antidepressant-like activity of the selective 5-HT6 receptor antagonist SB-399885 in rats
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Anna, Wesołowska
- Subjects
Male ,Sulfonamides ,Behavior, Animal ,Prazosin ,Benzazepines ,Motor Activity ,Antidepressive Agents ,Piperazines ,Rats ,Idazoxan ,Receptors, Serotonin ,Animals ,Dopamine Antagonists ,Serotonin Antagonists ,Rats, Wistar ,Sulpiride ,p-Chloroamphetamine ,Adrenergic alpha-Antagonists ,Injections, Intraperitoneal ,Stress, Psychological - Abstract
The mechanism of the antidepressant-like activity of the selective 5-hydroxytryptamine(6) (5-HT(6) receptor antagonist N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide (SB-399885) was studied in the forced swim test in rats. SB-399885 administered intraperitoneally at a single dose of 10 mg/kg potently shortened the immobility time in rats. That potential antidepressant-like effect of SB-399885 was not modified in animals with a lesion of the 5-HT system produced by p-chloroamphetamine (p-CA, 2 x 10 mg/kg). The anti-immobility effect of SB-399885 was blocked by the dopamine D(1)- and D(2)-like receptor antagonists SCH 23390 (0.063 mg/kg) and sulpiride (10 mg/kg), respectively, as well as by the alpha(2)-adrenoceptor antagonist idazoxan (4 mg/kg), but it was not changed by the alpha(1)-adrenoceptor antagonist prazosin (1 mg/kg). Neither sulpiride (10 mg/kg) or idazoxan (4 mg/kg) nor SCH-23390 (0.063 mg/kg) administered jointly with SB-399885 (10 mg/kg) noticeably changed the exploratory locomotor activity of rats evaluated by the open field test. The results described in the present paper indicate that the anti-immobility activity of SB-399885 is not connected with 5-HT innervation, and that D(1)- and D(2)-like receptors and alpha(2)-adrenoceptors are involved in this action.
- Published
- 2007
241. Kicking butts: smoking cessation update
- Author
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Wesam G, Yacoub and George, Reisz
- Subjects
Counseling ,Dopamine Uptake Inhibitors ,Quinoxalines ,Humans ,Smoking Cessation ,Benzazepines ,Varenicline ,Bupropion - Abstract
Tobacco is one of the most commonly abused drugs in the history of mankind. Smoking cessation has occupied a significant amount of research to help smokers quit to avoid the health risks. In this paper, we will discuss the methods available for smoking cessation. An evidence based approach will be used in a form directed towards both physicians and patients. We will review methods ranging from cold turkey to the latest addition to smoking cessation (varenicline).
- Published
- 2007
242. Fluorescence studies reveal heterodimerization of dopamine D1 and D2 receptors in the plasma membrane
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Agata Faron-Górecka, Joanna Andrecka, Maciej Kuśmider, Agnieszka Polit, Marta Dziedzicka-Wasylewska, and Zygmunt Wasylewski
- Subjects
Green Fluorescent Proteins ,Biology ,Biochemistry ,Fluorescence spectroscopy ,law.invention ,Cell Line ,Confocal microscopy ,law ,Dopamine ,Dopamine receptor D2 ,medicine ,Fluorescence Resonance Energy Transfer ,Humans ,Receptor ,Microscopy, Confocal ,Receptors, Dopamine D2 ,Receptors, Dopamine D1 ,HEK 293 cells ,Benzazepines ,Fluorescence ,Cell biology ,Förster resonance energy transfer ,Spectrometry, Fluorescence ,Spiperone ,Dimerization ,medicine.drug - Abstract
Evidence for hetero-oligomerization has recently been provided for various G protein-coupled receptors. In this paper, we have studied the possibility that dopamine D(1) and D(2) receptors physically interact with each other. Human dopamine D(1) and D(2) receptors were fluorescently tagged with derivatives of green fluorescence protein and transiently coexpressed in the membrane of human embryonic kidney 293 cells. Using qualitative fluorescence spectroscopy, as well as quantitative Förster resonance energy transfer (FRET) analysis, performed in a single cell by confocal microscopy and fluorescence lifetime microscopy, we show that dopamine D(1) and D(2) receptors can form hetero-oligomers in the plasma membrane. The degree of receptor protein-protein interaction is significantly enhanced by concomitant addition of D(1) and D(2) receptor subtype-specific agonists. Our investigations extend biochemical and electrophysiological studies and give insights into the regulation and synergistic mode of operation of dopamine receptors.
- Published
- 2006
243. Expression of behavioral sensitization to the cocaine-like fungicide triadimefon is blocked by pretreatment with AMPA, NMDA and DA D1 receptor antagonists
- Author
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R. Reeves, Mona Thiruchelvam, and Deborah A. Cory-Slechta
- Subjects
Male ,Serotonin ,medicine.drug_class ,Dopamine ,AMPA receptor ,Pharmacology ,Motor Activity ,Receptors, N-Methyl-D-Aspartate ,Piperazines ,chemistry.chemical_compound ,Mice ,Dopamine receptor D1 ,Cocaine ,Dopamine Uptake Inhibitors ,medicine ,Remoxipride ,Animals ,Receptors, AMPA ,Molecular Biology ,Sensitization ,Brain Chemistry ,SCH-23390 ,Behavior, Animal ,Dose-Response Relationship, Drug ,General Neuroscience ,Receptors, Dopamine D1 ,Body Weight ,Antagonist ,Benzazepines ,Triazoles ,Receptor antagonist ,Fungicides, Industrial ,Mice, Inbred C57BL ,medicine.anatomical_structure ,chemistry ,Dopamine Antagonists ,NBQX ,Central Nervous System Stimulants ,Neurology (clinical) ,Developmental Biology ,medicine.drug - Abstract
Triadimefon (TDF) is a triazole fungicide that blocks the reuptake of dopamine (DA), much like cocaine. A recent study in our laboratory found that intermittent injections of TDF led to robust locomotor sensitization in response to challenge TDF after a 2-week withdrawal period. The current study sought to determine whether the expression of TDF behavioral sensitization could be prevented by the DA D1-like receptor antagonist SCH 23390 (SCH), the DA D2-like receptor antagonist remoxipride (Rem), the competitive NMDA antagonist CPP, or the AMPA antagonist NBQX. Adult male C57/BL6 mice were injected with vehicle or 75 mg/kg TDF twice a week for 7 weeks, with locomotor activity measured periodically across the 14 doses. After a 2-week withdrawal period, mice were pretreated with SCH (0.015 mg/kg), Rem (0.3 mg/kg), CPP (2.5 mg/kg) or NBQX (10.0 mg/kg) followed 30 min later by vehicle or 75 mg/kg TDF and tested for the expression of TDF sensitization. Intermittent administration of TDF led to the development and robust expression of behavioral sensitization in terms of vertical activity. Pretreatment with SCH, NBQX and CPP successfully blocked the expression of vertical sensitization to TDF, while Rem pretreatment did not. All four antagonists, however, attenuated the neurochemical changes normally associated with TDF sensitization as measured 8 h after the 2-week TDF challenge. This paper reveals that NMDA, AMPA and DA D1-like receptors are necessary for the behavioral expression of sensitization to the fungicide triadimefon.
- Published
- 2004
244. Functional interaction between neuropeptide Y receptors and modulation of calcium channels in the rat hippocampus
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Arsélio P. Carvalho, João O. Malva, Ana P. Silva, and Caetana M. Carvalho
- Subjects
medicine.medical_specialty ,Glutamic Acid ,Biology ,Arginine ,Hippocampus ,Potassium Chloride ,Cellular and Molecular Neuroscience ,omega-Agatoxin IVA ,Cyclohexanes ,omega-Conotoxin GVIA ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Neuropeptide Y ,Rats, Wistar ,Receptor ,Long-term depression ,Voltage-gated Ca2+ channel ,Intracellular calcium ,Cells, Cultured ,Neurons ,Pharmacology ,Ionophores ,Voltage-dependent calcium channel ,Ionomycin ,Glutamate receptor ,Receptor Cross-Talk ,Benzazepines ,Calcium Channel Blockers ,Neuropeptide Y receptor ,Peptide Fragments ,Rats ,Receptors, Neuropeptide Y ,Endocrinology ,medicine.anatomical_structure ,Xanthenes ,Mechanism of action ,Metabotropic glutamate receptor ,Calcium ,Calcium Channels ,Neuron ,Glutamate release ,medicine.symptom ,Synaptosomes - Abstract
We investigated the functional interaction between neuropeptide Y (NPY) receptors using nerve terminals and cultured rat hippocampal neurons, and we evaluated the involvement of voltage-gated Ca2+ channels (VGCCs) in NPY receptors-induced inhibition of Ca2+ influx and glutamate release. The KCl-evoked release of glutamate from hippocampal synaptosomes was inhibited by 1 [mu]M NPY and this effect was insensitive to either BIBP3226 (Y1 receptor antagonist) or L-152,804 (Y5 receptor antagonist), but was sensitive to BIIE0246 (Y2 receptor antagonist). We could also pharmacologically dissect the NPY receptors activity by using Y1, Y2 and Y5 receptor agonists ([Leu31,Pro34]NPY, NPY13-36, NPY (19-23)-(Gly1,Ser3,Gln4,Thr6,Ala31,Aib32,Gln34)-pancreatic polypeptide (PP), respectively), and in all the cases we observed that these agonists could inhibited the KCl-induced release of glutamate. However, the selective and specific co-activation of both Y1 and Y2 or Y2 and Y5 receptors resulted in non-additive inhibition, and this effect was prevented in the presence of the Y2 antagonist, but was insensitive to the Y1 or Y5 receptor antagonist. Moreover, as we previously showed for Y1 receptors, we also observed that the activation of Y5 receptors inhibited the glutamate release in the dentate gyrus and CA3 subregion, without significant effect in the CA1 subregion of the hippocampus. The same qualitative results were obtained when we investigated the role of NPY Y1 and Y2 receptors in modulating the changes in [Ca2+]i due to KCl depolarisation in cultured hippocampal neurons. The inhibitory effect of nitrendipine (L-type VGCC blocker) or [omega]-conotoxin GVIA ([omega]-CgTx; N-type VGCC blocker) was not potentiated by the simultaneous activation of Y1 or Y2 receptors. Moreover, the exocytotic release of glutamate was inhibited by [omega]-agatoxin IVA ([omega]-Aga; P-/Q-type VGCC blocker), and this VGCC blocker did not potentiate Y1, Y2 or Y5 receptor-mediated inhibition of glutamate release. Also, the effect of ionomycin in inducing the exocytotic release of glutamate from hippocampal synaptosomes was insensitive to the activation of NPY receptors. In the present paper, we identified a role for NPY Y1, Y2 and Y5 receptors in modulating the exocytotic release of glutamate and the [Ca2+]i changes in the rat hippocampus. In conditions of co-activation, there appears to exist a physiological cross-talk between Y1 and Y2 and also between Y2 and Y5 receptors, in which Y2 receptors play a predominant role. Moreover, we also show that Y1 and Y2 receptors exert their inhibitory action by directly modulating L-, N-, and P-/Q-type VGCCs, whereas the inhibition of glutamate release mediated by the Y5 receptors seems to involve P-/Q-type VGCCs. http://www.sciencedirect.com/science/article/B6T0C-47RRRP0-C/1/70e1c3a1dbd6c37bea36062e48bf4a01
- Published
- 2003
245. Effects of nonpeptide V1a and V2 antagonists on blood pressure fast oscillations in conscious rats
- Author
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Nina Japundzic-Zigon
- Subjects
Male ,medicine.medical_specialty ,Vasopressin ,Receptors, Vasopressin ,Physiology ,Hypovolemia ,Stimulation ,Blood Pressure ,Hemorrhage ,Quinolones ,Piperidines ,Heart Rate ,Internal medicine ,Heart rate ,Internal Medicine ,medicine ,Animals ,Receptor ,Analysis of Variance ,Chemistry ,Antagonist ,General Medicine ,Benzazepines ,Pathophysiology ,Rats ,Blood pressure ,Endocrinology ,Mechanism of action ,Anesthesia ,medicine.symptom ,Antidiuretic Hormone Receptor Antagonists - Abstract
This paper describes the effects of vasopressin nonpeptide selective V1a (OPC-21268) and V2 (OPC-31260) antagonists on fast blood pressure (BP) oscillations in conscious non-haemorrhaged and haemorrhaged rats. Equidistant sampling at 20 Hz allowed direct spectral analysis of BP on 30 overlapping 2048 point-time series. In non-haemorrhaged rats, V1a antagonist (5 mg/kg; i.v) reduced BP and low-frequency (LF-BP) component while subsequent administration of V2 antagonist (1 mg/kg; i.v) reversed these changes and enhanced the very low-frequency (VLF-BP) component. In haemorrhaged rats (5-15 ml/kg/min) V2 antagonist pre-treatment enhanced the VLF-BP component during normotensive bleeding, while the V1a antagonist pre-treatment modified BP variability after hypotensive haemorrhage by enhancing the HF-SBP component. The results suggest that under normotensive conditions vasopressin by the stimulation of both V1a and V2 receptors buffers BP variability in the VLF-BP frequency domain. In addition, under hypotensive conditions vasopressin, by the stimulation of V1a receptors buffers the respiration-induced HF-BP oscillation.
- Published
- 2001
246. An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine
- Author
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N D, Evans, K R, Godfrey, M J, Chapman, M J, Chappell, L, Aarons, and S B, Duffull
- Subjects
Cardiotonic Agents ,Injections, Intravenous ,Administration, Oral ,Ivabradine ,Body Fluid Compartments ,Benzazepines ,Mathematical Computing ,Models, Biological ,Biotransformation - Abstract
The paper considers the structural identifiability of a parent-metabolite pharmacokinetic model for ivabradine and one of its metabolites. The model, which is linear, is considered initially for intravenous administration of ivabradine, and then for a combined intravenous and oral administration. In both cases, the model is shown to be unidentifiable. Simplification of the model (for both forms of administration) to that proposed by Duffull et al. (1) results in a globally structurally identifiable model. The analysis could be applied to the modeling of any drug undergoing first-pass metabolism, with plasma concentrations available from drug and metabolite.
- Published
- 2001
247. Determination of Dopamine D1 receptors in the human uveo-scleral tissue by light microscope autoradiography
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C, Cavallotti, N, Pescosolido, V, Pescosolido, and G, Iannetti
- Subjects
Adult ,Male ,Receptors, Dopamine D1 ,Dopamine D1 ,Uveo-scleral tissue ,Autoradiography ,Benzazepines ,Middle Aged ,Ligands ,Dopamine Antagonists ,Humans ,Ocular Hypertension ,Uvea ,Intraocular Pressure ,Sclera - Abstract
The aim of this paper is to clarify the distribution of Dopamine D1 (DA D1) receptors in the uveo-scleral tissue of human eyes with or without elevated intraocular pressure (IOP) and to study the relationships between DA D1 receptors and uveo-scleral tissue. Samples of human uveo-scleral tissue were taken from seven men undergoing eye surgery for a traumatic lesion of the anterior segment of the eye, without involvement of the iris-corneal angle and /or from eye donors. The subjects (in whom one eye bulb had been surgically enucleated) had been previously enrolled in our medical protocols because they suffered for increased IOP, while the eye donors (of both eye bulbs) had a normal IOP. Frozen sections from the uveo-scleral tissue were submitted to biochemical characterization and to morphological autoradiographic techniques for detection of DA-D1 receptors. [3H]-SCH-23390 was used as a ligand of Dopamine D1 receptors. [3H]-SCH 23390 was bound by sections of the human uveo-scleral tissue. The pharmacological profile of the binding was consistent with the labeling of D1 receptors. Light microscope analysis was used for localization of D1 receptors and revealed an accumulation of the radioligand in the human uveo-scleral tissue. In eyes with normal IOP there is a high reaction. The Bmax of radioligand decreases in the eyes with increased IOP. The possibility that dopaminergic receptors play a role in the controlling uveo-scleral tissue functions is suggested.
- Published
- 2001
248. Efficient synthesis of (S)-4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)- 3-oxo-2H-2-benzazepin-2-acetic acid (PHt-Hba(2,6-Cl2-Bn)-Gly-OH)
- Author
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J R, Casimir, D, Tourwé, K, Iterbeke, G, Guichard, and J P, Briand
- Subjects
Molecular Conformation ,Indicators and Reagents ,Phthalimides ,Dipeptides ,Benzazepines - Abstract
4-Amino-2-benzazepin-3-ones have proven very useful for studying the biologically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesulfonic acid (TFMSA) has been reported in the literature. However, when this procedure was applied to the preparation of Pht-Hba(Bn)-Gly-OH 8, many byproducts were formed and the yield of the desired aminobenzazepinones 7 and 8 was very low. We report in this paper an efficient methodology for the synthesis of Pht-Hba(2,6-Cl2-Bn)-Gly-OH 17 starting from the commercially available tyrosine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl2-Bn)-Gly-OH 15 is converted to the 1,3-oxazolidin-5-one 16 which then undergoes Friedel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-be nzazepin-3-one 17 in excellent yield.
- Published
- 2000
249. Tumor selective G2/M cell cycle arrest and apoptosis of epithelial and hematological malignancies by BBL22, a benzazepine
- Author
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Sumin Zhao, Neil L. Spector, Sydney Spector, Lourdes Alemane, Wenle Xia, Lys Hardy, and Alan Saluk
- Subjects
G2 Phase ,medicine.medical_specialty ,Mitosis ,Antineoplastic Agents ,Apoptosis ,Biology ,Prostate cancer ,Prostate ,Internal medicine ,medicine ,Tumor Cells, Cultured ,Humans ,Neoplasms, Glandular and Epithelial ,Receptor ,Multidisciplinary ,Cell Cycle ,Cancer ,Cell cycle ,Benzazepines ,Biological Sciences ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Cell culture ,Hematologic Neoplasms ,Cancer research - Abstract
Two distinct benzodiazepine binding sites have been identified, ( i ) a central site restricted to brain and ( ii ) a ubiquitously expressed mitochondrial binding site, the so-called peripheral-type benzodiazepine receptor (PBR). In this paper, we show that a benzazepine referred to as BBL22 (2-amino 9-chloro-7-(2-fluorophenyl)-5H-pyrimidol[5,4- d ][2]benzazepine), which is classified as a PBR ligand based on structure, induces arrest in G 2 /M phase of the cell cycle in human tumor cell lines of both epithelial and hematopoietic cellular origin. After G 2 /M arrest, several tumor types, notably prostate and certain breast cancer lines exhibited significant apoptosis. Ideally, cancer therapies should selectively target tumor cells while sparing normal cell counterparts. BBL22 exhibited such selectivity, as it did not affect the growth and survival of nonmalignant breast and prostate epithelial lines. Moreover, BBL22 demonstrated structural requirements for this selective antitumor activity as 11 structurally related PBR ligands, including high-affinity ligands Ro5–4864 and PK11195, failed to induce tumor cell growth arrest or apoptosis. The in vivo antitumor activity of BBL22 was examined in a human xenograft model of androgen-independent prostate cancer where BBL22 significantly reduced the growth of PC3 prostate tumors without eliciting overt toxicity. Identification of BBL22 represents a tumor selective therapeutic strategy for a variety of human tumors.
- Published
- 2000
250. The influence of endogenous dopamine levels on the density of [3H]SCH23390-binding sites in the brain of the honey bee, Apis mellifera L
- Author
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M T, Purnell, C J, Mitchell, D J, Taylor, I C, Kokay, and A R, Mercer
- Subjects
alpha-Methyltyrosine ,Dopamine ,Tryptophan ,Animals ,Brain ,Female ,Bees ,Benzazepines ,Social Behavior ,Tritium ,Chromatography, High Pressure Liquid ,Receptors, Dopamine - Abstract
This paper examines the relationship between endogenous dopamine (DA) levels and the density of [3H]SCH23390-binding sites in the brain of the adult worker honey bee. DA levels were reduced pharmacologically using a single 10 microl injection of either alpha-methyl-DL-p-tyrosine (AMT; 250 microg or 500 microg) or alpha-methyl-DL-tryptophan (AMTP; 250 or 500 microg) into the haemolymph of the bee. In all cases, maximum depletion of DA was observed 3 h after treatment, but in bees treated with AMTP (250 or 500 microg) or with 250 microg AMT, DA levels returned to normal within 24 h of treatment. Neither AMT nor AMTP was selective for DA: both drugs also reduced serotonin (5-hydroxytryptamine, 5HT) levels in the brain. However, AMTP was more effective than AMT at depleting 5HT, whereas for DA, the reverse was true. Depletion of DA levels, using 250 microg AMT, led to a dramatic decline in the levels of specific binding of [3H]SCH23390, defined in this study as binding in the presence of 5x10(-6) M cis-(Z)-flupentixol (see Ref. [28] ). In contrast, naturally occurring diel fluctuations in DA levels, identified in the optic lobes of the brain, and changes in brain DA levels resulting from queenlessness, had no significant effect on the density of [3H]SCH23390-binding sites in the brain of the bee. Overall, these results indicate that under normal physiological conditions, there is no direct link in honey bees between changes in endogenous brain DA levels and the density of D(1)-like receptors labelled by [3H]SCH23390.
- Published
- 2000
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