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The connection between smoking and Obstructive sleep apnea (OSA) is not yet clear. There are studies that have confirmed the effect of smoking on sleep disordered breathing, whereas others did not. Nicotine affects sleep, as smokers have prolonged total sleep and REM latency, reduced sleep efficiency, total sleep time, and slow wave sleep. Smoking cessation has been related with impaired sleep. The health consequences of cigarette smoking are well documented, but the effect of smoking cessation on OSA has not been extensively studied. Smoking cessation should improve OSA as upper airway oedema may reduce, but there is limited data to support this hypothesis. The impact of smoking cessation pharmacotherapy on OSA has been studied, especially for nicotine replacement therapy (NRT). However, there are limited data on other smoking cessation medications as bupropion, varenicline, nortriptyline, clonidine, and cytisine. The aim of this review was to explore the current evidence on the association between smoking and OSA, to evaluate if smoking cessation affects OSA, and to investigate the possible effects of different pharmacologic strategies offered for smoking cessation on OSA. [ABSTRACT FROM AUTHOR]

Background: Testicular torsion is a pathological condition which needs emergency surgical intervention. However, after surgical reperfusion, oxidative stress factors cause to germ cell apoptosis. The study was planned to evaluate the efficacy of simultaneous use of Cyclosporine A (CsA) and Nortriptyline (Nort) to repair testicular damages in an experimental torsion/detorsion (T/D) rat model. Methods: Male rats (n = 112) were allocated into 7 groups 16 each in; (Group 1); Control group, (Group 2); T/D group, (Group 3–4); CsA 1 and 5 mg/kg, (Group 5–6); Nort 2 and 10 mg/kg and (Group 7); concurrent group, CsA (1 mg/kg) + Nort (2 mg/kg). Right uni-lateral torsion was inducted by twisting testis 720 degrees in the clockwise direction for 1 h. For short-term and mid-term studies, lipid peroxidation, antioxidant enzyme activities, caspase-3 level, histopathological changes and germ cell apoptosis were evaluated. Moreover, in long-term investigation, semen analysis was performed. Results: After T/D induction, testis abnormalities both functional and structural were appeared. Pre- and post-treatment with CsA and Nort, separately, reduced MDA and caspase-3 levels, normalized antioxidant levels, ameliorate tissue injury and improved sperm criteria. Conclusion: The antioxidant and anti-apoptotic characteristics of CsA and Nort and their protective effects have been shown in our study. Concurrent administration of CsA and Nort in selected low-dose indicated a significant positive effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress in short-term, apoptosis, and histologic changes in mid-term, as well as semen criteria in the long-term appraisal. [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate the feasibility of a nortriptyline (NT) formulation for transdermal administration and to assess the usefulness of an estimated kinetic parameter (kout) using the in vitro infinite dose technique to predict in vivo plasma levels when used in combination with pharmacokinetic parameters. To do so, a simple one-compartment model was used to describe the transport of a permeant across a membrane (skin). This model provides relatively simple expressions for the amount of permeant in the skin, the cumulative amount of permeant that crosses the skin, and the flux of permeant, for both the infinite and the finite dose regimens. Transdermal administration of the formulated NT gel to rats resulted in plasma levels of approximately 150 ng/mL between 8 and 30 h post-administration. These levels were higher than the minimum concentration of 40 ng/mL recommended for smoking cessation therapy and slightly higher than the upper limit of the therapeutic range for the treatment of depression in humans. The one-compartment model used to describe transport across the skin was connected to a two-compartment pharmacokinetic model used to predict NT plasma concentrations in rats using the kout determined in vitro and the values of other pharmacokinetic parameters obtained in vivo. The predicted concentrations were close to the observed plasma levels and the time profiles were similar for both types of data. These results show the usefulness of the kout parameter determined in vitro to predict plasma concentrations of drugs administered percutaneously. [ABSTRACT FROM AUTHOR]

With the thought and strong hope of uniqueness and challenging characteristic highlights and importance of nanofibrous mats (NFMs) along with cyclodextrins (CDs) that having a significant opportunity, chances and handling a vital role in hostile to bacterial activities. For the most part, CDs are utilized to upgrade the antibacterial activity through the improvement of solubility, stability, and etc., to any molecule which can bring inside the CDs cavity via the formation of inclusion complexes. Polymer-mediated electrospun nanofibrous mats (PAN NFMs) are utilized as a nanocarrier for antibacterial activity in this article, utilizing nortriptyline (NP) as a reference molecule. As a result, NP forms an inclusion complex with β-Cyclodextrin (β-CD). As a result, the PAN NFMs are able to absorb it, thereby consolidating the complex NP on the nanofibrous surface. Additionally, the soaking of PAN NFMs in NP solution without β-CD was performed for comparison. To characterize the nanofibrous mats of NP/PAN and NP:β-CD-ICs/PAN NFMs, UV absorption, FTIR, Raman, XRD, and SEM techniques were used. The antibacterial activity of NP and NP:β-CD-ICs have been tried against positive control antibiotics by the disc diffusion method. Thus, the action has been improved for NP:β-CD-ICs/PAN NFMs over NP/PAN NFMs because of the solubility upgraded for the NP by the complexation of β-CD. [ABSTRACT FROM AUTHOR]

Background: Real-world effectiveness of interventions in palliative care need to be systematically quantified to inform patient/clinical decisions. Neuropathic pain is prevalent and difficult to palliate. Tricyclic antidepressants have an established role for some neuropathic pain aetiologies, but this is less clear in palliative care. Aim: To describe the real-world use and outcomes from amitriptyline or nortriptyline for neuropathic pain in palliative care. Design: An international, prospective, consecutive cohort post-marketing/phase IV/pharmacovigilance/quality improvement study of palliative care patients with neuropathic pain where the treating clinician had already made the decision to use a tricyclic antidepressant. Data were entered at set times: baseline, and days 7 and 14. Likert scales graded benefits and harms. Setting/participants: Twenty-one sites (inpatient, outpatient, community) participated in six countries between June 2016 and March 2019. Patients had clinician-diagnosed neuropathic pain. Results: One hundred and fifty patients were prescribed amitriptyline (110) or nortriptyline (40) of whom: 85% had cancer; mean age 73.2 years (SD 12.3); mean 0–4 scores for neuropathic pain at baseline were 1.8 (SD 1.0). By day 14, doses of amitriptyline were 57 mg (SD 21) and nortriptyline (48 mg (SD 21). Fifty-two (34.7%) patients had pain improvement by day 14 (amitriptyline (45/110 (43.3%); nortriptyline (7/40 (18.9%)). Thirty-nine (27.7%) had new harms; (amitriptyline 29/104 (27.9%); nortriptyline 10/37 (27.0%); dizziness (n = 23), dry mouth (n = 20), constipation (n = 14), urinary retention (n = 10)). Benefits without harms occurred (amitriptyline (26/104 (25.0%); nortriptyline (4/37 (10.8%)). Conclusions: Benefits favoured amitriptyline while harms were similar for both medications. [ABSTRACT FROM AUTHOR]

ObjectiveMal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy.Study designProspective review.SettingAmbulatory setting at a tertiary care medical center.MethodsClinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale.ResultsFifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy.ConclusionManagement of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine.Level of evidence4 Laryngoscope, 127:1670-1675, 2017.

Introduction: Due to the complexity of symptoms in major depressive disorder (MDD), the majority of depression scales fall short of accurately assessing a patient's progress. When selecting the most appropriate antidepressant treatment in MDD, a multidimensional scale such as the Hamilton Depression Rating scale (HAM-D) may provide clinicians with more information especially when coupled with unidimensional analysis of some key factors such as depressed mood, altered sleep, psychic and somatic anxiety and suicidal ideation etc. Methods: HAM-D measurements were carried out in patients with MDD when treated with two different therapeutic interventions. The prespecified primary efficacy variables for the study were changes in score from baseline to the end of the 12 weeks on HAM-D scale (i.e., ≤ 8 or ≥50% response). The study involved three assessment points (baseline, 6 weeks and 12 weeks). Results: Evaluation of both the absolute HAM-D scores and four factors derived from the HAM-D (depressed mood, sleep, psychic and somatic anxiety and suicidal ideation) revealed that the latter showed a greater promise in gauging the anti-depressant responses. Conclusion: The study confirms the assumption that while both drugs may improve several items on the HAM-D scale, the overall protocol may fall short of addressing the symptoms diversity in MDD and thus the analysis of factor (s) in question might be more relevant and meaningful. [ABSTRACT FROM AUTHOR]

Objective: There is limited evidence that adding an antidepressant to electroconvulsive therapy (ECT), compared with ECT monotherapy, improves outcomes. We aimed to determine whether the addition of nortriptyline to ECT enhances its efficacy and prevents post‐ECT relapse. Methods: We conducted a randomized, double‐blind, placebo‐controlled trial (RCT). Patients with major depressive disorder and an indication for ECT received either nortriptyline or placebo during a bilateral ECT course. Outcome measures were mean decrease in Hamilton Rating Scale for Depression (HRSD) score, response, remission, and time to response and remission. Patients who attained remission participated in a 1‐year follow‐up study with open‐label nortriptyline. Outcome measures were relapse and time to relapse. Results: We included 47 patients in the RCT. In the nortriptyline group, 83% showed response, 74% attained remission, and the mean decrease in HRSD score was 21.6 points. In the placebo group these figures were, respectively, 81% (p = 0.945), 73% (p = 0.928) and 20.7 points (p = 0.748). Thirty‐one patients participated in the follow‐up study. In patients who had received nortriptyline during the RCT, 47% relapsed at a mean of 34.2 weeks. Patients who had received placebo showed similar treatment results. In both study phases, no statistically significant differences between the nortriptyline and the placebo group were found. Conclusion: In our sample of severely depressed patients who were often medication resistant and suffering from psychotic depression, the addition of nortriptyline to ECT did not enhance its efficacy or prevent post‐ECT relapse. Encouragingly, even in these patients ECT was highly effective and relapse rates were relatively low. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathic pain (DNP) is a common complication of diabetes and has a profound effect on patients quality of life. Therefore. The purpose of the present study was to compare the analgesic effects of duloxetine and nortryptiline in the management of patients with diabetic neuropathy. Methods: This was a randomized, double-blind, parallel-group, placebo-controlled trial in subjects with a proven diagnosis of DM and suffered from neuropathic pain. Patients were recruited in this study from 20 February 2016 (first patient, first visit) to 22 June 2017 (last patient, last visit), including 5 weeks follow-up. A diagnosis of DNP was based on history, clinical examination, Nerve conduction velocity and Diabetic neuropathy symptom score (more than one point). Results: Both drugs reduced pain when compared with placebo. A significant VAS reduction from 6.4 at baseline to 3.75 at endpoint was observed in the duloxetine group. However, there was no significant difference in the efficacy between nortriptyline and duloxetine based on patientchr('39')s visual analogue scale (VAS) (p>0.05). No clinically significant changes or serious adverse events were found among treatment groups including changes in vital signs, laboratory assessments, physical examination or electrocardiograms. The decrease in the mean pain intensity was significantly greater in the duloxetine and nortriptyline group compared to the placebo group both in the primary analysis and in the by-visit analysis (p

Background and Aims: Headache is the most common reason for referring to a physician. Therapeutic approaches of this condition include the treatment of the acute attacks and prevention of future attacks. In this regard, this study aimed to investigate the effect of three medications, namely levetiracetam, sodium valproate, and nortriptyline on the control of migraine headaches in patients with migraine referred to Birjand Neurology Clinic, Birjand, Iran. Materials and Methods: This study was conducted based on a quasi-experimental research method. According to the physician, 120 migraine patients were divided into three groups of levetiracetam (a daily dose of 250 mg), sodium valproate (500 mg), and nortriptyline (25 mg) for four weeks. A questionnaire was used to collect the demographic characteristics of the patient. The data were analyzed using SPSS software (version 16) through the chi-square tets, paired t-test, and ANOVA. Results: The patients (n=120) were divided into three groups of 40 cases per group. The mean age of the patients was 33±11 years, and the majority of the cases (53.3%) were female. In total, 46.7% of the cases had severe headache before taking these medications; however, none of them experienced severe headache after taking the medicine. It should be noted that 77.5% of the patients experienced mild headache. The group taking levetiracetam showed the greatest decrease in headache intensity (P=0.01). Conclusion: According the results, levetiracetam appears to be more effective than the other two medications, especially sodium valproate, in terms of the mitigation of different degrees of headache.

IntroductionDue to the complexity of symptoms in major depressive disorder (MDD), the majority of depression scales fall short of accurately assessing a patient's progress. When selecting the most appropriate antidepressant treatment in MDD, a multidimensional scale such as the Hamilton Depression Rating scale (HAM-D) may provide clinicians with more information especially when coupled with unidimensional analysis of some key factors such as depressed mood, altered sleep, psychic and somatic anxiety and suicidal ideation etc.MethodsHAM-D measurements were carried out in patients with MDD when treated with two different therapeutic interventions. The prespecified primary efficacy variables for the study were changes in score from baseline to the end of the 12 weeks on HAM-D scale (i.e., ≤ 8 or ≥50% response). The study involved three assessment points (baseline, 6 weeks and 12 weeks).ResultsEvaluation of both the absolute HAM-D scores and four factors derived from the HAM-D (depressed mood, sleep, psychic and somatic anxiety and suicidal ideation) revealed that the latter showed a greater promise in gauging the anti-depressant responses.ConclusionThe study confirms the assumption that while both drugs may improve several items on the HAM-D scale, the overall protocol may fall short of addressing the symptoms diversity in MDD and thus the analysis of factor (s) in question might be more relevant and meaningful.

Introduction: Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors in the clinic. The preferred first-line therapy is a medical treatment with dopamine agonists (DAs), mainly cabergoline, to reduce serum prolactin levels, tumor volume, and mass effect. However, in some cases, patients have displayed DA resistance with aggressive tumor behavior or are faced with recurrence after drug withdrawal. Also, currently used therapeutics have notorious side effects and impair the life quality of the patients. Methods: Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerges to exhibit essential roles in the behavior and progression of prolactinomas; in this work, we integrated mRNA- and microRNA (miRNA)-level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma. Results: We identified 8 drug candidates through drug repurposing based on mRNA-miRNA-level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven repurposed drugs including 5-fluorocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing the PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and Western blotting. Discussion: We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA-level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of the PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments. [ABSTRACT FROM AUTHOR]

• Inflammatory markers correlated differentially with specific depressive symptoms. • 17 of 27 inflammatory markers decreased significantly during antidepressant treatment. • We found no correlation between inflammatory markers and overall response. • Changes in inflammation correlated with response on neurovegetative symptoms. • We found no correlation between inflammatory markers and 10-year prognosis. Inflammation may correlate with a specific subgroup of depression and differential antidepressant response, but no trial has studied changes of many inflammatory markers over several time points and evaluated symptom-specific antidepressant response and long-term prognosis. We performed secondary analyses among 90 outpatients with moderate-severe depression (71% female, mean age 38 years) treated for 26 weeks with escitalopram or nortriptyline. We measured 27 pro- and anti-inflammatory markers at week 0, 8, 12, and 26 and calculated composite inflammation scores. Three depression rating scales were applied and symptom dimensions of depression calculated. Via Danish nationwide registers, 10 years follow-up were included on psychiatric hospital contacts, indicating relapse. Pearson correlation analyses were performed between baseline inflammatory markers and depressive symptom severity, mixed effects models during the 26-week trial, and Cox regression analyses for the register-based outcomes, adjusted for age, sex, BMI, and smoking. Baseline inflammatory markers correlated with differential severity on specific symptom dimensions but not with overall depression severity. A total of 17 of 27 inflammatory markers decreased significantly during treatment. We found no correlation between baseline nor change in inflammatory markers nor composite inflammation scores with differential treatment response on the MADRS, but small correlations between changes in inflammatory markers and differential response on neurovegetative symptoms. Findings were similar among 59 treatment-naïve patients. Inflammatory markers were not associated with differential risks for 10-year relapse. These findings support the importance of studying specific depressive symptoms to further explore the correlation between inflammation with differential antidepressant response in a subgroup of depression. Clinical Trial Registration number: GENDEP is registered at EudraCT2004–001723–38 (http://eudract.emea.europa.eu) and ISRCTN03693000 (www.controlled-trials.com). [ABSTRACT FROM AUTHOR]

It has proven that the presence of different chemicals can affect the succession patterns of necrophagous insects. A comprehensive study was designed on the effects of nortriptyline, diazinon, and aluminum phosphate on arthropod's succession and diversity on cadavers. Sixteen rabbits in two groups were used as a model in this study, 12 of them were treated with the drugs and were placed in two habitats (sun and shade) based on the study design. For each group, one cage was considered as control. Insects were collected twice a day from the cadavers and identified. In total, 549 necrophagous insects from five families, were collected from all the carcasses. Chrysomya albiceps was the dominant insect on all cadavers, expect for one treated with diazinon, in which it was displaced by Dermestes frischii. The highest number of insects were collected on the sixth day for all cadavers. The majority were collected from the shaded cages. Generally, the species diversity was higher for all the cadavers treated with the drugs compared to the control cadavers. The results showed that the presence of diazinon in the cadaver can repel necrophagous insects, on the contrary nortriptyline seems to attract more species/specimen. [ABSTRACT FROM AUTHOR]

Introduction: An antidepressant nortriptyline potentiates glucocorticoid (GC) action with synergistic suppression of inflammatory mediator release, but the precise molecular mechanism is unknown. Materials and methods: Peripheral blood cells from patients with chronic obstructive pulmonary disease (COPD) (n = 21) were incubated with nortriptyline (1 μM or 10 μM), budesonide (10 nM), or their combinations, followed by stimulation with phorbol myristate acetate (PMA) and ionomycin. Cytokine production, glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2) and histone H4 acetylation of K8 (HAT) expression, p65 NF-kB and p38 mitogen- activated protein kinase (p38 MAPK) phosphorylation in NK (CD3-CD56+) and NKT-like (CD3+CD56+) cells were analyzed by flow cytometry. Results: We observed that nortriptyline (10 μM) significantly attenuated the effects of PMA/ionomycin on the synthesis of interferon γ (IFNγ), interleukin 4 (IL-4), and IL-8, expression of GRβ and HAT, as well as p65 NF-kB and p38 MAPK phosphorylation in NK and NKT-like cells, whereas nortriptyline (1 μM) only inhibited IL-4 production by NK and NKT-like cells. Discussion: The combination of nortriptyline (10 μM) and budesonide decreased IFNγ, tumor necrosis factor α, IL-4, IL-8, and GRβ expression, as well as phosphorylated p38 MAPK and p65 NF-κB levels by NK and NKT-like cells above that of budesonide alone. Furthermore, the same association of drugs enhanced HDAC2 expression in NK and NKT-like cells. Conclusion: Collectively, our results show that nortriptyline might enhance GC function through modulation of HAT, HDAC2, GRβ, phospho-p38 MAPK expression. These data provide a strong rationale for combining nortriptyline with budesonide to treat COPD. [ABSTRACT FROM AUTHOR]

You Zhai,1,2 Lihua Wu,1,2 Yunliang Zheng,1,2 Minglan Wu,1,2 Yujie Huang,1,2 Qian Huang,1,2 Jianzhong Shentu,1– 3 Qingwei Zhao,1,2 Jian Liu1,2 1Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Jian LiuResearch Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People’s Republic of ChinaTel +86 571 87236537Fax +86 571 87214223Email lindaliu87@zju.edu.cnPurpose: This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug.Materials and Methods: A randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC0-t, AUC0-∞), the peak plasma concentration (Cmax), the time to achieve Cmax (Tmax), and the elimination half-life (t1/2). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs).Results: The values of t1/2 and Tmax for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of Cmax, AUC0–t, and AUC0-∞ between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events.Conclusion: This study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.Keywords: bioequivalence, pharmacokinetics, amitriptyline hydrochloride, nortriptyline

Background: Gastric ulcer is among the most serious stomach disorder universally. Several effective drugs are employed in the management of this disease, although there have been adverse effects in some cases. The aim of this study was to investigate the effect of nortriptyline to protect against gastric lesions, induced by indomethacin or cold-stress in rats. Methods: Gastric lesions were induced by oral indomethacin (30 mg/kg) or cold-shock at 2-4°C. Animals were pre-treated with 5, 10 or 20 mg/kg nortriptyline. After 4hr of exposure to indomethacin or cold shock, the stomach was removed for histological examinations and the levels of enzymatic and non-enzymatic oxidative stress markers were determined in the tissue samples. Results: The results showed that nortriptyline at 20 mg/kg significantly restored the activity of the oxidative stress markers, such as Superoxide Dismutase (SOD) and Catalase (CAT) enzymes. It also decreased the tissue Malondialdehyde (MDA) concentration. In addition, nortriptyline at 20 mg/kg, ameliorated the gastric tissue damages caused by indomethacin or the cold shock. Conclusion: The results suggest that improvement in gastric mucosal lesions can be mediated by nortriptyline pretreatment, which is likely due to its antioxidant property.

There has been an increase in the use of antidepressant drugs owing to significant economic challenges across the globe. Consequently, the increase in production of such drugs has impacted pharmaceutical pollution of industrial wastewaters discharged into the environment. Hence, there is a need to develop efficient adsorbents for antidepressant wastewater treatment. The impregnation of silver nanoparticles on biowaste was found to be highly effective in the treatment of oil-polluted water but has not been utilized in the adsorption of drugs. Herein, the dataset associated with the adsorption of antidepressants onto Ananas Comosus Peel (AP) and Silver nanoparticle-loaded Ananas Comosus peel (AgAP) was reported. Batch adsorption methodology was used to study the effect of antidepressant concentration (10–50 mg/L), sonication time (10–120 min), temperature (300–320 K) and adsorbent dosage (0.10–0.18 g). The concentration of antidepressant (Nortriptyline) in solution before and after adsorption was determined by the UV-Spectrophotometer at a maximum wavelength of 239 nm. The isotherm dataset was obtained from the Langmuir, Freundlich, Temkin and Dubinin-Raduskevich models, while kinetic data was evaluated by the pseudo-first order-pseudo-second-order, film diffusion and intraparticle diffusion rate equations. The data on the thermodynamics and adsorbent reusability were also provided. The dataset showed an adsorption capacity of 3.27 mg/g and 4.74 mg/g for AP and AgAP, respectively. The dataset is important to material and environmental scientists and revealed the efficiency of AP and AgAP in the treatment of antidepressant wastewater.

Objective: Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for individuals experiencing recurrent migraine episodes. Our study aimed to compare the efficacy and safety profiles of venlafaxine and nortriptyline in the prophylactic management of migraine., Methods: In this single-center, randomized, double-blind clinical trial, 210 migraine patients were allocated into two groups in a 1:1 ratio. One group received venlafaxine (37.5 mg, orally twice daily), while the other group administered nortriptyline (25 mg, orally once daily). A neurologist documented (1) headache intensity using the Visual Analog Scale (VAS) and 6-point Behavioral Rating Scale (BRS-6), (2) headache frequency (per month), and (3) headache duration (in hours) of participants on days 0, 45, and 90 of the intervention., Results: Following the 90-day intervention, a significant decrease was observed in VAS, BRS-6, frequency, and duration of headaches within both groups (all with p-values <0.001). No difference in VAS, BRS-6, or headache durations was observed between the two groups after 45 and 90 days of treatment (all p-values > 0.05). Although the headache frequency exhibited no difference between the groups after 45 days (p-value = 0.097), a significantly lower frequency in the venlafaxine group was observed at day 90 of the intervention (p-value = 0.011). The reductions in attack parameters in the 0-45- and 0-90-day intervals did not meet statistical significance between the two groups (p-values > 0.05). 77.0 % of the participants in the venlafaxine group and 79.2 % in the nortriptyline group experienced a minimum of 50 % improvement in all attack parameters. Venlafaxine demonstrated a statistically significant lower incidence of adverse reactions in comparison to nortriptyline (p-value = 0.005). A total of 33 adverse drug reactions were documented in the venlafaxine group and 53 in the nortriptyline group, with insomnia observed in the former and xerostomia in the latter as the most prevalent side effects., Conclusions: Venlafaxine and nortriptyline demonstrate clinically significant and comparable therapeutic efficacy for migraine patients in reducing the intensity, frequency, and duration of headache attacks. Venlafaxine may be preferred to nortriptyline in the context of migraine preventive treatment under comparable conditions due to its lower incidence of adverse effects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Persistent idiopathic dentoalveolar pain (PIDAP) is a type of disease that, despite affecting thousands of people globally, negatively impacts patients' quality of life because of its unknown cause. Notably, the disease has a high prevalence rate and is primarily prone to middle-aged and senior individuals. Efforts have been made to gain the understanding needed for the accurate diagnosis and prompt treatment of PIDAP cases. This case report discusses the challenges faced in diagnosing and managing PIDAP after dental implants. The present study involved the case of a 62-year-old male patient, previously operated on for an implant at position #11, who suffered from chronic pain but no specific cause could be identified. We used an evaluation strategy to gain insights into the patient's illness, including antibiotic treatment, crown replacement, and continued pain. We prescribed nortriptyline 10 mg, and there was an improvement. This finding suggests that nortriptyline 10 mg QHS eliminates chronic pain., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Prince Sultan Medical Military City issued approval 841. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alturki et al.)

Background and Objectives: - The safety of Pregabalin and Nortriptyline have been proved individually in chronic low backache with radiculopathy. However, there are limited number of studies comparing the tolerability of Pregabalin and Nortriptyline in chronic low backache with radiculopathy. Hence the present study is designed to determine the tolerability of Pregabalin versus Nortriptyline. It is an prospective observational study. Methods: - Patients with chronic low backache with radiculopathy 15-60 years of age without specific cause and significant neurological deficit were included. Patients were followed up at 2 and 4 weeks and their side effect were noted. Results: - There was no statistical difference between pregabalin and nortriptyline groups in terms of visual analogue scale for pain score, from baseline to 2 weeks and from baseline to week 4. The incidence of side effects were statistically less in the nortriptyline group compared to pregabalin group. From the results of the present study it can be concluded that both pregabalin and nortriptyline are effective in the treatment of chronic low backache with radiculopathy with radicular pain but incidence of adverse events are more with the pregabalin compared to nortriptyline. Conclusion: - Anticonvulsants and TCAs are very effective in moderate to severe pain while the other drugs like NSAIDs and opioids are more effective in mild to moderate pain. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is a chronic dermatologic condition presenting as multiple papulonodular lesions occurring with intense pruritus. Though numerous agents (topical, systemic, phototherapy and biological drugs) have been tried, the outcomes are variable. Objectives: The aim of this study was to assess the role of topical and systemic therapies in primary PN by comparing the Pruritus Grading System (PGS) score at baseline and 1 month post-therapy. Materials and Methods: Of 86 diagnosed cases of PN, 49 cases of primary PN were clinically graded by Pruritus Grading System Score (PGSS), and assessed histopathologically by IHC staining (STAT-1, 3, and 6). Apart from topical agents, oral nortriptyline (mild grade), methotrexate (moderate grade) and thalidomide (severe grade) were administered, whereas doxepin was administered for itching. The PGSS was assessed after 1 month of therapy. Results: Among 49 patients of PN, the majority of patients showed a significant decrease in PGSS (P = <0.001) in 1 mont, which correlated with STAT-6 expression. The combination of different topical and oral agents resulted in a statistically significant change in severity, though individual drugs did not achieve statistically significant results. Conclusion: A combination of selected oral and topical agents can effectively control the severity of PN within one month, and this was found to correlate with STAT 6 expression. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of nortriptyline and tolerability of side effects in the treatment of neurogenic cough. Secondary goal is to evaluate the association between laryngeal asymmetry and clinical response to nortriptyline. Study Design: Retrospective case series. Materials and Methods: Consecutive patients diagnosed with neurogenic cough at a quaternary care specialty hospital from 2001 to 2020 were identified. Subjects <18 years old, not treated with nortriptyline, did not have a nasolaryngoscopic examination and were lost to follow-up were excluded. Charts were reviewed for demographic information, clinical history, nasolaryngoscopic findings, medication dosage, side effects, and follow-up time. Results: Forty-two patients met inclusion and exclusion criteria, 7 males and 35 females with an average age of 56.5 (±13.1) years. There were 26/36 (72.2%) responders and 10/36 (27.8%) non-responders; 6 patients stopped nortriptyline due to side effects and were not included in the response comparison. Laryngeal asymmetry was present in 36/42 (85.7%) patients. No factors related to laryngeal asymmetry were significantly different between responders and non-responders. Medication tolerance was observed in 3/42 (7.1%) patients. Side effects were reported in 16/42 (38.1%) patients. The most common side effects were sedation 9/42 (21.4%) and xerostomia 3/42 (7.1%). Conclusion: Nortriptyline is effective for treating neurogenic cough with 72% of patients reporting improvement in cough. Evidence of laryngeal asymmetry was not associated with better treatment response. Although 38% experienced side effects, the majority of patients continued nortriptyline despite side effects. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate the feasibility of a nortriptyline (NT) formulation for transdermal administration and to assess the usefulness of an estimated kinetic parameter (kout) using the in vitro infinite dose technique to predict in vivo plasma levels when used in combination with pharmacokinetic parameters. To do so, a simple one-compartment model was used to describe the transport of a permeant across a membrane (skin). This model provides relatively simple expressions for the amount of permeant in the skin, the cumulative amount of permeant that crosses the skin, and the flux of permeant, for both the infinite and the finite dose regimens. Transdermal administration of the formulated NT gel to rats resulted in plasma levels of approximately 150 ng/mL between 8 and 30 h post-administration. These levels were higher than the minimum concentration of 40 ng/mL recommended for smoking cessation therapy and slightly higher than the upper limit of the therapeutic range for the treatment of depression in humans. The one-compartment model used to describe transport across the skin was connected to a two-compartment pharmacokinetic model used to predict NT plasma concentrations in rats using the kout determined in vitro and the values of other pharmacokinetic parameters obtained in vivo. The predicted concentrations were close to the observed plasma levels and the time profiles were similar for both types of data. These results show the usefulness of the kout parameter determined in vitro to predict plasma concentrations of drugs administered percutaneously.

The tricyclic antidepressant amitriptyline is frequently prescribed but its use is limited by its narrow therapeutic range and large variation in pharmacokinetics. Apart from interindividual differences in the activity of the metabolising enzymes cytochrome P450 (CYP) 2D6 and 2C19, genetic polymorphism of the hepatic influx transporter organic cation transporter 1 (OCT1) could be contributing to interindividual variation in pharmacokinetics. Here, the impact of OCT1 genetic variation on the pharmacokinetics of amitriptyline and its active metabolite nortriptyline was studied in vitro as well as in healthy volunteers and in depressive disorder patients. Amitriptyline and nortriptyline were found to inhibit OCT1 in recombinant cells with IC50 values of 28.6 and 40.4 µM. Thirty other antidepressant and neuroleptic drugs were also found to be moderate to strong OCT1 inhibitors with IC50 values in the micromolar range. However, in 35 healthy volunteers, preselected for their OCT1 genotypes, who received a single dose of 25 mg amitriptyline, no significant effects on amitriptyline and nortriptyline pharmacokinetics could be attributed to OCT1 genetic polymorphism. In contrast, the strong impact of the CYP2D6 genotype on amitriptyline and nortriptyline pharmacokinetics and of the CYP2C19 genotype on nortriptyline was confirmed. In addition, acylcarnitine derivatives were measured as endogenous biomarkers for OCT1 activity. The mean plasma concentrations of isobutyrylcarnitine and 2-methylbutyrylcarnitine were higher in participants with two active OCT1 alleles compared to those with zero OCT1 activity, further supporting their role as endogenous in vivo biomarkers for OCT1 activity. A moderate reduction in plasma isobutyrylcarnitine concentrations occurred at the time points at which amitriptyline plasma concentrations were the highest. In a second, independent study sample of 50 patients who underwent amitriptyline therapy of 75 mg twice daily, a significant trend of increasing amitriptyline plasma concentrations with decreasing OCT1 activity was observed (p = 0.018), while nortriptyline plasma concentrations were unaffected by the OCT1 genotype. Altogether, this comprehensive study showed that OCT1 activity does not appear to be a major factor determining amitriptyline and nortriptyline pharmacokinetics and that hepatic uptake occurs mainly through other mechanisms.

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.