Search

Parkinson's disease (PD) is a progressive neurological ailment with a slower rate of advancement that is more common in older adults. The biggest risk factor for PD is getting older, and those over 60 have an exponentially higher incidence of this condition. The failure of the mitochondrial electron chain, changes in the dynamics of the mitochondria, and abnormalities in calcium and ion homeostasis are all symptoms of Parkinson's disease (PD). Increased mitochondrial reactive oxygen species (mROS) and an energy deficit are linked to these alterations. Levodopa (L-DOPA) is a medication that is typically used to treat most PD patients, but because of its negative effects, additional medications have been created utilizing L-DOPA as the parent molecule. Ergot and non-ergot derivatives make up most PD medications. PD is successfully managed with the use of dopamine agonists (DA). To get around the motor issues produced by L-DOPA, these dopamine derivatives can directly excite DA receptors in the postsynaptic membrane. In the past 10 years, two non-ergoline DA with strong binding properties for the dopamine D2 receptor (D2R) and a preference for the dopamine D3 receptor (D3R) subtype, ropinirole, and pramipexole (PPx) have been developed for the treatment of PD. This review covers the most recent research on the efficacy and safety of non-ergot drugs like ropinirole and PPx as supplementary therapy to DOPA for the treatment of PD. [ABSTRACT FROM AUTHOR]

In patients with Parkinson's disease (PD), dopamine replacement therapy with dopamine D2/D3 receptor agonists induces impairments in decision-making, including pathological gambling. The neurobiological mechanisms underlying these adverse effects remain elusive. Here, in a mouse model of PD, we investigated the effects of the dopamine D3 receptor (D3R)-preferring agonist pramipexole (PPX) on decision-making. PD model mice were generated using a bilateral injection of the toxin 6-hydroxydopamine into the dorsolateral striatum. Subsequent treatment with PPX increased disadvantageous choices characterized by a high-risk/high-reward in the touchscreen-based Iowa Gambling Task. This effect was blocked by treatment with the selective D3R antagonist PG-01037. In model mice treated with PPX, the number of c-Fos-positive cells was increased in the external globus pallidus (GPe), indicating dysregulation of the indirect pathway in the corticothalamic-basal ganglia circuitry. In accordance, chemogenetic inhibition of the GPe restored normal c-Fos activation and rescued PPX-induced disadvantageous choices. These findings demonstrate that the hyperactivation of GPe neurons in the indirect pathway impairs decision-making in PD model mice. The results provide a candidate mechanism and therapeutic target for pathological gambling observed during D2/D3 receptor pharmacotherapy in PD patients. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, which promotes a sustained inflammatory environment in the central nervous system. Regulatory T cells (Tregs) play an important role in the control of inflammation and might play a neuroprotective role. Indeed, a decrease in Treg number and function has been reported in PD. In this context, pramipexole, a dopaminergic receptor agonist used to treat PD symptoms, has been shown to increase peripheral levels of Treg cells and improve their suppressive function. The aim of this work was to determine the effect of pramipexole on immunoregulatory Treg cells and its possible neuroprotective effect on human dopaminergic neurons differentiated from human embryonic stem cells. Methods: Treg cells were sorted from white blood cells of healthy human donors. Assays were performed with CD3/CD28‐activated and non‐activated Treg cells treated with pramipexole at concentrations of 2 or 200 ng/mL. These regulatory cells were co‐cultured with in vitro‐differentiated human dopaminergic neurons in a cytotoxicity assay with 6‐hydroxydopamine (6‐OHDA). The role of interleukin‐10 (IL‐10) was investigated by co‐culturing activated IL‐10‐producing Treg cells with neurons. To further investigate the effect of treatment on Tregs, gene expression in pramipexole‐treated, CD3/CD28‐activated Treg cells was determined by Fluidigm analysis. Results: Pramipexole‐treated CD3/CD28‐activated Treg cells showed significant protective effects on dopaminergic neurons when challenged with 6‐OHDA. Pramipexole‐treated activated Treg cells showed neuroprotective capacity through mechanisms involving IL‐10 release and the activation of genes associated with regulation and neuroprotection. Conclusion: Anti‐CD3/CD28‐activated Treg cells protect dopaminergic neurons against 6‐OHDA‐induced damage. In addition, activated, IL‐10‐producing, pramipexole‐treated Tregs also induced a neuroprotective effect, and the supernatants of these co‐cultures promoted axonal growth. Pramipexole‐treated, activated Tregs altered their gene expression in a concentration‐dependent manner, and enhanced TGFβ‐related dopamine receptor regulation and immune‐related pathways. These findings open new perspectives for the development of immunomodulatory therapies for the treatment of PD. [ABSTRACT FROM AUTHOR]

Pramipexole, a D2/D3 dopamine receptor agonist, is used to treat the motor symptoms of Parkinson's disease, caused by degeneration of the dopaminergic nigrostriatal pathway. There are three paradoxes associated with its mode of action. Firstly, stimulation of D2/D3 receptors leads to neuronal inhibition, although pramipexole does not inhibit but promotes some dopamine-modulated functions, such as locomotion and reinforcement. Secondly, another dopamine-modulated function, arousal, is not promoted but inhibited by pramipexole, leading to sedation. Thirdly, pramipexole-evoked sedation is associated with an increase in pupil diameter, although sedation is expected to cause pupil constriction. To resolve these paradoxes, the path from stimulation of D2/D3 receptors to the modification of dopamine-modulated functions has been tracked. The functions considered are modulated by midbrain dopaminergic nuclei: locomotion – substantia nigra pars compacta (SNc), reinforcement/motivation – ventral tegmental area (VTA), sympathetic activity (as reflected in pupil function) – VTA; arousal – ventral periaqueductal grey (vPAG), with contributions from VTA and SNc. The application of genetics-based molecular techniques (optogenetics and chemogenetics) has enabled tracing the chains of neurones from the dopaminergic nuclei to their final targets executing the functions. The functional neuronal circuits linked to the D2/D3 receptors in the dorsal and ventral striata, stimulated by inputs from SNc and VTA, respectively, may explain how neuronal inhibition induced by pramipexole is translated into the promotion of locomotion, reinforcement/motivation and sympathetic activity. As the vPAG may increase arousal mainly by stimulating cortical D1 dopamine receptors, pramipexole would stimulate only presynaptic D2/D3 receptors on vPAG neurones, curtailing their activity and leading to sedation. [ABSTRACT FROM AUTHOR]

Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12–15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward. [ABSTRACT FROM AUTHOR]

Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating episodes, obesity, or metabolic syndrome, for example). Although the history of SRED encompasses more than six decades, public awareness and even the awareness of the mental health specialists of this disorder is very limited, a phenomenon that hinders the development of research in this field. Therefore, a systematic review based on PRISMA 2020 guidelines explored the available evidence for SRED found in four electronic databases (PubMed, Cochrane Collaboration, Google Scholar, and Clarivate/Web of Science). A number of 94 primary and secondary reports were retrieved, investigating aspects regarding the risk factors, epidemiology, clinical data and differential diagnosis, epidemiology, structured evaluation, and treatment of SRED. Based on the results of these reports, Z-drugs, but also certain benzodiazepines, antidepressants, antipsychotics, and psychostimulants may trigger the onset of SRED. Psychiatric and neurologic disorders have also been associated with SRED, either as risk factors or comorbid conditions. Cerebral glucose metabolism dysfunctions, neurotransmitter dysfunctions, and genetic factors have been invoked as pathogenetic contributors. Structured assessment of SRED is possible, but there is a dearth of instruments dedicated to this purpose. Data on the prevalence and treatment of SRED exist, but good-quality epidemiological studies and clinical trials are still missing. In conclusion, future research is expected to address the shortcomings of SRED exploration by creating the conditions for better quality and larger group clinical research. The need for such investigation is granted by the importance of this pathology and its negative functional consequences. [ABSTRACT FROM AUTHOR]

One of the biggest problems in the treatment of idiopathic Parkinson's disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for idiopathic Parkinson's disease that requires years to accumulate enough lost neurons for the onset of motor symptoms. This single-neuron degeneration model is based on the excessive formation of aminochrome during neuromelanin synthesis that surpass the neuroprotective action of the enzymes DT-diaphorase and glutathione transferase M2-2, which prevent the neurotoxic effects of aminochrome. Although the neurotoxic effects of aminochrome do not have an expansive effect, a stereotaxic injection of this endogenous neurotoxin cannot be used to generate a preclinical model in an animal. Therefore, the aim of this review is to evaluate the strategies for pharmacologically increasing the expression of DT diaphorase and GSTM2-2 and molecules that induce the expression of vesicular monoamine transporter 2, such as pramipexole. [ABSTRACT FROM AUTHOR]

Infantile dystonia-parkinsonism type 2 (PKDYS2) is a rare inherited autosomal recessive movement disorder with onset in infancy. The disease is associated with a mutation in the solute carrier family 18 member A2 gene (SLC18A2). There are reports of trials with dopaminergic drugs and the condition of patients given levodopa almost always worsens and dopamine agonists give varying degrees of benefit to some. Here, we report a PKDYS2 patient with a new variant in the SLC18A2 gene who underwent multiple trials of pharmacotherapy. The abnormalities in development and neurological examination of the case were first noted at the age of 2 months, and after a series of treatment attempts (e.g., with antiepileptics) and diagnostic procedures, the diagnosis of PKDYS2 was determined when whole exome sequencing (WES) at age 6, revealed a homozygous pathologic variant NM_003054.4:c.1107dup, p.(Val370Serfs ∗ 91) in the SLC18A2 gene. The patient then received treatment with multiple dopaminergic drugs (e.g., levodopa, pramipexole, and methylphenidate). The patient with PKDYS2 harbored a new variant in SLC18A2. The phenotype of the patient resembles that of some previously reported patients with PKDYS2. The patient received minor benefits from certain dopaminergic drugs, such as pramipexole, but side effects led to the discontinuation of tested medications. [ABSTRACT FROM AUTHOR]

Background: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG). Methods: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed. Results: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07–5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77–5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP. Conclusion: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to systematically compare the effectiveness, safety, and costs of different anti‐Parkinson drugs (APDs). Methods: This is a multi‐center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs‐related adverse events. Results: A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56–355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088–0.135/day for levodopa/benserazide; $0.070–0.126/day for carbidopa/levodopa; $0.112–0.138/day for piribedil; $0.290–0.332/day for pramipexole; $0.229–0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031). Conclusions: Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model. [ABSTRACT FROM AUTHOR]

In Parkinson's disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson's model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy. [ABSTRACT FROM AUTHOR]

Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct. [ABSTRACT FROM AUTHOR]

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson's disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings. [ABSTRACT FROM AUTHOR]

Background: There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity. Objectives: The objective was to determine if P2B001 (a fixed, low‐dose, extended‐release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole‐ER. Methods: This was a 12‐week, double‐blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole‐ER 0.6 mg or rasagiline‐ER 0.75 mg), or commercial doses of pramipexole‐ER titrated to optimal dose (1.5–4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole‐ER. Results: P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were −2.66 (95% CI, −4.33 to −1.00) versus pramipexole‐ER 0.6 mg (P = 0.0018) and − 3.30 (95% CI, −4.96 to −1.63) versus rasagiline‐ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole‐ER (mean, 3.2 mg), but significantly less worsening in daytime‐sleepiness (ESS treatment difference: −2.66 [95% CI, −3.50 to −1.81]; P < 0.0001). P2B001 was well‐tolerated with fewer sleep‐related and dopaminergic adverse events than titrated doses of pramipexole‐ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects. Conclusions: P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole‐ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once‐daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The article discusses the use of long-term repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD), highlighting two case studies of patients who maintained remission through extended rTMS therapy. Topics discussed include the effectiveness of maintenance rTMS, individualized treatment protocols, and the impact of comorbid conditions on therapy outcomes.

Copyright of Ege Journal of Medicine is the property of Ege University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: This study aims to clinically evaluate the impulse control disorders (ICDs) encountered in treating Parkinson's disease. Method: This is a retrospective analysis between 2010 and 2022. We retrieved the medical records of all patients diagnosed with idiopathic Parkinson's disease. The demographic and clinical findings were recorded. ICDs constituted a specific item in the examination, and each one (compulsive shopping, compulsive eating, pathological gambling, hypersexuality, punding, dopamine dysregulation syndrome, and hobbyism) was noted separately. Results: In the study period, we identified 1824 patients (56.2% men, n = 1025). The mean age was 70.5 ± 11.9 years. In the cohort, 128 (7%) patients with Parkinson's disease had one or more ICDs. The ICDs were compulsive shopping, punding/hobbyism, compulsive eating, hypersexuality, pathological gambling, and dopamine dysregulation syndrome. When we compared patients with and without ICDs, patients with ICDs were younger (p ≤ 0.001), and the men/women ratio was higher in this group with ICDs. Although the mean daily pramipexole dose was higher in patients with ICDs, mean daily long-acting pramipexole dose was only 1.4 ± 0.92 mg/day. Conclusion: The significant findings in this study were (i) the lower frequency of ICDs (7%); (ii) the common occurrence of compulsive shopping, punding/hobbyism, and compulsive eating; and (iii) the development of ICDs under relatively lower doses of pramipexole. We suggest that ICDs in Parkinson's disease should be associated with a personal trait with dopamine agonists, and potential electrophysiological or genetic markers of this trait warrant further analysis to avoid treatment in these patients. [ABSTRACT FROM AUTHOR]

Copyright of Turkiye Klinikleri Journal of Forensic Medicine & Forensic Sciences / Türkiye Klinikleri Adli Tıp ve Adli Bilimler Dergisi is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, orally disintegrating tablets (ODT) of pramipexole dihydrochloride monohydrate (PPX) was developed with direct compression method by using ready-to-use excipients Parteck® ODT, Pharmaburst® 500, Ludiflash®, F-Melt®, and Prosolv® Easytab SP for pediatric restless leg syndrome (RLS). The formulated ODTs were circular in shape with a total weight of around 100 mg, which was appropriate for pediatric use. In spite of very low content of the drug, content uniformity could be obtained successfully in accordance to the pharmacopoeial specification with a satisfactory mechanical strength in terms of hardness and friability. However, formulations based on Parteck® ODT and Ludiflash® could not achieve a disintegration time <30 s according to in vitro disintegration test, which was also supported by the simulated wetting test. The optimal ODTs based on Pharmaburst® 500, F-Melt® and Prosolv® Easytab SP were further evaluated for in vitro dissolution study. A very fast release of the drug was observed with these formulations that reached a peak value in 10 min., which was superior than that of the reference conventional tablet formulation of PPX. As a result, pediatric orally disintegrating tablets of PPX were successfully formulated with Pharmaburst® 500, F-Melt® and Prosolv® Easytab SP by using direct compression method with suitable characteristics, which can be further studied to use in pediatric RLS. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1ß. [ABSTRACT FROM AUTHOR]

Pramipexole, a dopaminergic agonist, has rarely been implicated as a cause of hyponatremia in patients with Parkinson's disease (PD). Pramipexole-induced stimulation of anti-diuretic hormone results in euvolemic hyponatremia. This is often neglected, and hyponatremia may lead to worsening of the motor symptoms with PD and an unnecessary increase in dopaminergic medications, causing disabling dyskinesias. This case report describes a patient with young-onset PD who developed newonset hyponatremia due to pramipexole-induced syndrome of inappropriate anti-diuretic hormone within 3 months of starting the drug. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA ismore potent than another. We performed a systematic review and network meta-analysis to evaluate the eficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD). Methods: SixNEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed. Results: A total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890). Conclusions: In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially asmonotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD. [ABSTRACT FROM AUTHOR]

Background: Restless legs syndrome (RLS) is characterized by an unpleasant or painful sensation generally localized to lower limbs and relieved by movement. Its pathogenesis is hypothesized to involve the dopaminergic system, also in the light of the response of RLS to ex adiuvantibus treatment with dopamine agonists. DNAJC12 deficiency is a recently identified inherited metabolic disease coupling hyperphenylalaninemia to deficient dopaminergic and serotoninergic neurotransmission, due to the combined impairment of the three aromatic amino acids' (i.e., phenylalanine, tyrosine, and tryptophan) hydroxylases. DNAJC12 deficiency was reported in 43 patients so far, presenting with wide spectrum of clinical symptoms. Case presentation results: Here, we report RLS as a novel clinical manifestation of DNAJC12 deficiency, occurring in two adults while on treatment with l-dopa at longitudinal follow-up. The adjunct of low-dose pramipexole was effective in both patients to treat RLS. Besides, this treatment also allowed an improvement of dopaminergic homeostasis, as evidenced by clinical amelioration and stabilization of a peripheral short prolactin profile (a tool to indirectly evaluate dopaminergic homeostasis). Discussion: Besides including RLS as a new treatable clinical manifestation of DNAJC12, these observations may suggest the opportunity of a selective screening for DNAJC12 deficiency in patients with idiopathic RLS. [ABSTRACT FROM AUTHOR]

Pain is one of the most frequent causes for patients to seek medical care. It interferes with daily functioning and affects the quality of life of the patient. There is a clear need to investigate nonopioid or non‐nonsteroidal anti‐inflammatory drug alternatives for the treatment of pain. In this study, we determined the effect of acute pre‐ and posttreatment with pramipexole (PPX), a dopamine D2/D3 selective agonist, on formalin 1%‐induced acute and long‐lasting nociceptive behavior sensitivity in rats. Moreover, we sought to investigate whether the antiallodynic and antihyperalgesic effect induced by PPX was mediated through the nuclear factor‐κB (NF‐kB) signaling pathway. Moreover, acute systemic pretreatment with PPX (1 and 3 mg/kg, ip) suppressed the formalin‐induced nociceptive behavior during both phases of the formalin test and the development of formalin‐induced secondary mechanical allodynia and hyperalgesia in both paws. Acute systemic posttreatment with PPX (3 mg/kg, ip) reverted the formalin‐induced long‐lasting secondary mechanical allodynia and hyperalgesia. Furthermore, PPX inhibits the protein expression of NF‐κB–p65 and the levels of tumor necrosis factor‐α and interleukin‐1β in the spinal cord of animals with secondary mechanical allodynia and hyperalgesia induced by formalin. These data suggest that PPX has a potential role in producing anti‐inflammatory activity. Moreover, the antiallodynic and antihyperalgesic effects induced by PPX can be mediated through the NF‐kB signaling pathway. [ABSTRACT FROM AUTHOR]

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting. [ABSTRACT FROM AUTHOR]

Background: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. Methods: This comprehensive systematic review and meta-analysis of observational studies on pramipexole–antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. Results: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8–69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. Conclusions: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression. [ABSTRACT FROM AUTHOR]

Background: Levodopa monotherapy and combination therapy with non‐ergot dopamine agonists (DAs; pramipexole, ropinirole, and rotigotine) are commonly used in patients with Parkinson's disease (PD). Changes in prescription preferences for each DA were reported previously; however, information regarding the selection of individual DAs is insufficient. Aim: To investigate the reasons for selecting each DA. Methods: This observational study used a Japanese claims database (April 2008–July 2017). The percentage of patients prescribed each DA was analyzed by year (2010–2017). The change in DA prescriptions and prevalence of comorbidities before DA initiation or before replacement with another DA were analyzed from 2013. Results: The database included 50,408 patients with PD who received ≥1 levodopa and/or DA prescriptions. Pramipexole was the most popular DA; however, its prescription has decreased since 2012. Ropinirole prescriptions remained relatively unchanged, while that of rotigotine tended to increase since its launch in 2013 and recently surpassed that of ropinirole. The most frequent pattern of change (both in addition and replacement) was from pramipexole to rotigotine. Differences were observed in the prevalence of comorbidities among DAs. Conclusion: Pramipexole was often prescribed at the beginning of the study period; the decrease in its prescription frequency might be mainly related to new DA options. The frequent change from pramipexole to rotigotine might be associated with the different DA characteristics, which may be a factor influencing the choice of a specific DA. [ABSTRACT FROM AUTHOR]

Purpose: Pramipexole (Prami) is renowned as one of the most widely used drugs in the treatment of Parkinson's disease. This study aimed to prepare slow-release nanofibers of Prami to reduce (or control) the release rate of the drug from the formulation. Methods: For this purpose, polyvinyl alcohol (PVA)/carboxymethylcellulose (CMC) nanofibers loaded with Prami were fabricated using the electrospinning technique and characterized using scanning electron microscopy (SEM) and infrared spectroscopy (FTIR). A test has been conducted to evaluate the swelling of the formulations and an HPLC method has been used to assess the effect of both co-electrospinning with polycaprolactone (PCL) nanofibers and cross-linking using glutaraldehyde (GA) vapors on the release kinetics. Results: The results showed that the co-electrospun nanofibers cross-linked by 12-h exposure to GA vapor exhibited slow release compared to non-hybrid and non-cross-linked fibers. The cell viability assay using the MTT test showed that the nanofibers were cytocompatibility regarding SFIF-PI 44 cell line. The hybrid cross-linked nanofibers were placed in the gelatin shell capsule, and the dissolution profile of the drug in the capsules was investigated. Conclusions: These results indicated that using nanofibers as the carrier encapsulated in the conventional capsule dosage form can be considered as a new formulation to reduce the used excipients and ease of production. [ABSTRACT FROM AUTHOR]

This article presents two case studies of painful legs and moving toes syndrome (PLMT), a rare syndrome characterized by pain in the lower limbs and involuntary movements of the toes. The article discusses the symptoms, diagnostic evaluations, and treatment of two patients with PLMT. Additionally, the article discusses a case study of a patient with obstructive sleep apnea (OSA) and periodic limb movement disorder (PLMD), highlighting the underdiagnosis of PLMD and potential treatments. The aim of the article is to raise awareness of PLMD as a distinct neurological condition and its association with atypical leg pain. [Extracted from the article]

Background and objective: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. Methods: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients' disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. Results: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). Conclusion: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality. [ABSTRACT FROM AUTHOR]

A drug-excipient interaction impurity associated with the degradation process of pramipexole was isolated. The impurity was detected during the stability study of pramipexole extended-release tablets. It was found at a relative retention time of 0.88 with respect to pramipexole, using the pramipexole gradient HPLC-UV detection method described in the USP. The structure of the impurity was identified and fully characterized using high resolution mass spectrometry, IR and NMR techniques, as presented herein. The degradation impurity was identified as (S)-N2-(methoxymethyl)-N6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine. The drug-excipient interaction mechanism of its formation was proposed. An efficient and straightforward synthetic approach was developed to prepare the degradation impurity to confirm its proposed degradation pathway and structure. [ABSTRACT FROM AUTHOR]

Background and objective: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magnesium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED. Methods: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesium oxide. While others in the control group merely received a placebo. Patients' disease severity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted. Results: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001). Conclusion: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality. [ABSTRACT FROM AUTHOR]

Verbal fluency impairment is common in patients with Parkinson's disease (PD), but the effect of drugs on verbal fluency in PD patients has not been comprehensively evaluated. We conducted a network meta-analysis based on four online databases to compare the effect of drugs on verbal fluency in PD patients. This study was performed and reported according to PRISMA-NMA guidelines. In total, 6 out of 3707 articles (three RCTS and three cross-sectional studies) covering eight drug regimens were included (five for letter fluency, five for semantic fluency). In terms of letter fluency, the ranking of the overall efficacy of included drug regimens was: levodopa, levodopa combined with pramipexole, rotigotine, cabergoline, pramipexole, pergolide, but no drug regimen presented a significant advantage over the others. In terms of semantic fluency, the ranking of the overall efficacy of included drug regimens was: rotigotine, levodopa, cabergoline, pergolide, pramipexole, among which, levodopa alone (SMD = 0.93, 95%CI: 0.28–1.59) and rotigotine alone (SMD = 1.18, 95%CI: 0.28–2.09) were statistically superior to pramipexole, while no significant difference was identified between all the other drug regimens. Levodopa and rotigotine seem to be more appropriate choices for PD patients with verbal fluency impairment. Further study is needed to illustrate the efficacy of drugs on verbal fluency in PD patients. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a common neurodegenerative disease that rarely occurs in young people. Therefore, cases where pregnancy and Parkinson's disease occur together are very rare and pregnant patients receiving anti-Parkinsonian therapy are rarely presented as case reports in the literature. We report a case of a 36-year-old pregnant woman with a 5 year history of early onset Parkinson's disease who was exposed to levodopa/benserazide plus pramipexole treatment during the first 8 weeks, and levodopa/benserazide treatment until the 37th gestational week. The patient was followed up by the perinatology specialist at regular intervals throughout her pregnancy. No fetal anomaly was detected in the follow-ups. She gave birth to a healthy baby girl by an uncomplicated cesarean delivery. Evidence based data on the most appropriate treatment of Parkinson's disease in pregnancy have not been found in the literature. Larger studies are needed on this subject. [ABSTRACT FROM AUTHOR]

Background Patients with Parkinson's disease (PD) show impaired performance in taste recognition tests, which suggests a possible dopaminergic influence on gustatory functioning. To experimentally test this hypothesis, we assessed whether pharmacological manipulation of dopaminergic signaling in healthy volunteers can affect performance in a standardized taste recognition test. Methods Physically and mentally healthy volunteers (n = 40, age 18–43 years) were randomly allocated to treatment with either pramipexole or placebo using a double-blind, parallel-group design. After 12 to 15 days of treatment (dose titrated up from 0.25 mg/d of pramipexole salt to 1.0 mg/d), taste recognition performance was assessed using a standardized and validated assay (taste strip test). Additionally, visual analogue scale ratings of subjective pleasantness and disgustingness of taste samples were obtained. Results Compared with the placebo group, participants receiving pramipexole showed significantly higher total recognition accuracy (medianpramipexole = 14.0, medianplacebo = 13.0, U = 264.5, P  = .04). This was driven by a higher sensitivity for taste in the pramipexole group. Exploratory analysis of pleasantness and disgustingness ratings of appetitive (sweet) vs aversive (bitter) stimuli suggested that pramipexole treatment was associated with overall blunted hedonic responses, but this effect did not survive the inclusion of nausea (a side effect of treatment) as a covariate in the analysis. Conclusions Healthy volunteers who received subacute pramipexole treatment exhibited higher taste recognition performance compared with the placebo group. This finding is consistent with a proposed role of the dopaminergic system in gustatory functioning and could have important theoretical and clinical implications. [ABSTRACT FROM AUTHOR]

The article discusses novel treatments for bipolar depression. Topics covered include several published guidelines that include recommendations for treating acute bipolar depression, bipolar depression treatments according to their levels of evidence, and evidence-based assessment tools to use when standard treatments have not worked.

Copyright of Dilemas Contemporáneos: Educación, Política y Valores is the property of Dilemas Contemporaneos: Educacion, Politica y Valores and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment from the patient's perspective. Studies demonstrating the treatment effect of pramipexole on QoL remain inconclusive. This study aims to evaluate the effect of pramipexole on QoL in patients with PD by conducting a systematic review and meta-analysis of existing clinical trials.Methods: A systematic literature search of PubMed, Embase and the Cochrane Library was performed from inception to 30 April 2022 to identify randomised, placebo-controlled trials of patients with idiopathic PD receiving pramipexole, who reported a change from baseline in their QoL as measured by the 39-item Parkinson's Disease Questionnaire (PDQ-39). Risk of bias was independently assessed by two reviewers using the Cochrane Collaboration's tool for bias assessment.Results: Of 80 eligible articles screened, six trials consisting of at least 2000 patients with early or advanced PD were included. From the synthesis of all six selected trials, a significant mean change from baseline in the PDQ-39 total score of -2.49 (95% CI, -3.43 to -1.54; p < 0.0001) was observed with pramipexole compared with placebo. A trend toward improvement in QoL was consistently observed among patients who received optimal doses of pramipexole (≥ 80% of the study population on 1.5 mg dosage), regardless of disease severity (advanced versus early) or baseline QoL levels.Conclusion: This meta-analysis provides evidence for the potential treatment benefit of pramipexole in improving QoL in patients with PD. [ABSTRACT FROM AUTHOR]

Background and Objective: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD).Methods: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks.Results: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated.Conclusion: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a severe disease of brain damage accompanied by blood–brain barrier (BBB) dysfunction. The BBB is composed of brain microvascular endothelial cells (BMECs), astrocyte terminus, pericytes, and a basement membrane. Tight junction proteins expressed by BMECs play important roles in preserving BBB integrity. Pramipexole is a selective dopamine agonist applied for treating Parkinson's disease and has been recently claimed with neuroprotective capacity. This study will further explore the impact of Pramipexole on tight junctions and BBB integrity to provide the potential treatment strategy for TBI-induced BBB damage. The TBI model was established in mice and was identified by the promoted brain water content, declined Garcia scores, reduced latency of the rotarod test, aggravated pathological changes in the brain cortex, and excessively released inflammatory factors. After treatment with Pramipexole, the neurofunctional deficits, behavioral disability, and aggravated pathological changes were dramatically reversed, accompanied by the alleviated BBB permeability, and upregulated occludin, an important tight junction protein. TBI model cells were established by the scratching bEnd.3 cells method. Cells were stimulated with 10 and 20 μM Pramipexole, followed by exposure to TBI. Increased fluorescence intensity of FITC-dextran, reduced value of TEER, and downregulated occludin and KLF2 were observed in TBI-exposed cells, all of which were greatly reversed by 10 and 20 μM Pramipexole. Furthermore, in KLF2-silenced bEnd.3 cells, the protective ability of Pramipexole against endothelial permeability and the expression level of occludin were dramatically abolished. Collectively, our results suggest that Pramipexole protected against TBI-induced BBB dysfunction by mediating KLF2. [ABSTRACT FROM AUTHOR]

Pramipexole (PMXL) belongs to the benzothiazole class of aromatic compounds and is used in treating Parkinson's disease; however, overdosage leads to some abnormal effects that could trigger severe side effects. Therefore, it demands a sensitive analytical tool for trace level detection. In this work, we successfully developed an electrochemical sensor for the trace level detection of PMXL, using the voltammetric method. For the analysis, graphitic carbon nitride (gCN) was opted and synthesized by using a high-temperature thermal condensation method. The synthesized nanoparticles were employed for surface characterization, using transmission electron microscopy (TEM), X-ray diffraction (XRD), and atomic force microscopy (AFM) techniques. The electrochemical characterization of the material was evaluated by using the electrochemical impedance spectroscopy (EIS) technique to evaluate the solution–electrode interface property. The cyclic voltammetry (CV) behavior of PMXL displayed an anodic peak in the forward scan, indicating that PMXL underwent electrooxidation, and an enhanced detection peak with lower detection potential was achieved for gCN-modified carbon paste electrode (gCN·CPE). The influence of different parameters on the electrochemical behavior was analyzed, revealing the diffusion governing the electrode process with an equal number of hydronium ions and electron involvement. For the fabricated gCN·CPE, good linearity range was noticed from 0.05 to 500 µM, and a lower detection limit (LD) of 0.012 µM was achieved for the selected concentration range (0.5 to 30 µM). Selectivity of the electrode in PMXL detection was investigated by conducting an interference study, while the tablet sample analysis demonstrates the sensitive and real-time application of the electrode. The good recovery values for the analysis illustrate the efficiency of the electrode for PMXL analysis. [ABSTRACT FROM AUTHOR]

The article discusses the comorbidity of narcissistic personality disorder (NPD) and major depressive disorder (MDD). Topics include prevalence estimates of NPD in clinical samples, a case of a major depressive episode with suicidal ideation in a middle-aged man with fragile narcissism, and usefulness of a variety of diagnostic approaches in assessing the comorbidity of MDD and NPD.

Background: Depression is one of the most common neuropsychiatric symptoms in Parkinson;s disease (PD). There is little evidence to guide depression treatment in these patients. The aim of this study was to compare citalopram and pramipexole in reducing depressive symptoms in patients with PD. Materials and Methods: In the present 8-week randomized trial, we compared the efficacy of pramipexole versus citalopram in the treatment of depression in PD patients. For this purpose, 44 PD patients with depression randomly received open-label oral citalopram tablets or pramipexole and their depression, quality of life, and daytime sleepiness scores were evaluated at baseline and after the 8-week trial period. Results: The median age of the patients was 64 years, and about 85% of them were male in both groups. The Beck Depression Inventory score, Parkinson's disease summary index (PDSI), and Epworth Sleepiness Scale were significantly decreased (P < 0.05) in both citalopram and pramipexole groups throughout this period and without significant difference (P > 0.05) between these two groups, except for PDSI score which showed significant improvement in pramipexole group compared with citalopram group (P < 0.0001, r = 0.319). There were neither serious adverse effects nor treatment discontinuation due to the adverse effects. Conclusion: The results indicated that both citalopram and pramipexole were effective in the alleviation of depression and improving the quality of life in PD patients; however, pramipexole was seemed to be slightly more beneficial on quality of life in these patients. Therefore, pramipexole seems to be an effective treatment for depression in addition to its benefits for motor symptoms of PD patients. [ABSTRACT FROM AUTHOR]

Adenosine A1 and A2A receptors are expressed in striatal projection neurons (SPNs). A1 receptors are located in direct (dSPN) and indirect SPNs (iSNP). A2A receptors are only present in iSPNs. Dopamine D2 receptors are also expressed in iSPNs and interactions between D2 and A2A receptors have received attention. iSPNs activity increases during parkinsonism (PD) and A2A receptors may be responsible by enhancing Ca2+ currents (iCa2+). Therefore, A2A receptors blockade is a therapeutic approach. We asked whether A2A receptors need the interaction with D2 receptors (D2R) to exert their actions. By using isolated and identified iSPNs to avoid indirect influences, we show that D2R action habilitates A2A receptors (A2AR) modulation. iCa2+ through voltage gated Ca2+ channels (CaV) was used as a signal to observe this interaction. Voltage-clamp recordings in acutely dissociated iSPNs, current-clamp recordings in slices and calcium imaging in transgenic A2A-Cre mice, showed that D2R reduction in iCa2+ endows A2AR to restore iCa2+ on iSPNs showing an antagonistic interaction between D2 and A2A receptors. A2A receptors were blocked by the antagonist istradefylline, however, this blockade differed in control and dopamine-depleted iSPNs: istradefylline reduced D2R modulation in parkinsonian animals as compared to controls. Calcium imaging recordings show that istradefylline occludes D2R actions in the parkinsonian circuitry and this effect depends on the order of drugs application. Thus, while D2 activation enables A2A receptors action, blockade of A2AR induces a reduction in the action of D2 agonists, confirming a complex interaction. Summary Statement: A2A receptor required previous D2 receptor activation to modulate Ca2+ currents. Istradefylline decreases pramipexole modulation on Ca2+ currents. Istradefylline reduces A2A + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study on the effectiveness of pramipexole in the treatment of acute pancreatitis induced by L-arginine in a rat model. Topics mentioned include the suppression of inflammasome signaling, the level of serum lipase and amylase, the changes in pancreatic histopathology, and the evaluation of oxidative stress and inflammatory biomarkers.

Introduction Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole vs placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. Methods and analysis PAX-D will assess effectiveness in the short-term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to week 12 post-randomisation measured using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Performance on the decision-making task will be measured at week 0, week 2 and week 12. Secondary outcomes include anhedonia, anxiety and health economic measures including quality of life, capability, well-being and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. Discussion Pramipexole is a promising augmentation agent for TRD and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with TRD. [ABSTRACT FROM AUTHOR]

In this study, we fabricated an effective and sensitive DNA biosensor based on flower‐like Pt/NiCo2O4 modified carbon paste electrode (FL‐Pt/NiCo2O4/CPE) for detection of pramipexole (PPX). Spectrophotometry, differential pulse voltammetry (DPV) and docking methods were employed to evaluate the interaction of DNA‐PPX. Moreover, the DPV technique was chosen to monitor the electrochemical response of guanine on the DNA biosensor. The relationship between the concentration of PPX and the oxidation signal of guanine was linear in the range of 0.4 to 310.0 μM and a limit of detection (LOD) of 0.09 μM was calculated. [ABSTRACT FROM AUTHOR]

Despite levodopa's superior efficacy in reducing the motor symptoms of Parkinson's disease (PD), its risk to induce motor complications requires consideration of the pros and cons of initiating treatment with levodopa-sparing strategies. The current drive toward early levodopa monotherapy is primarily driven by safety and tolerability concerns with dopamine agonists and only mild efficacy of other available approaches. Recently, P2B001, a novel once-daily combination of low-dose, extended-release formulations of pramipexole and rasagiline (0.6 mg and 0.75 mg respectively), has entered clinical development. In this drug evaluation, we review the preclinical and current clinical data for P2B001 and its components. The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa. Plain Language Summary: Parkinson's disease is the fastest growing neurologic disorder across the globe. Once diagnosed, it is now generally agreed that there is no clinical rationale to postpone symptomatic treatment in people who develop Parkinson's-related disability. There are three main treatment options available for use in early Parkinson's disease: levodopa, dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors. Of these, there is a current push toward using levodopa as the main first-line therapy. This is primarily because of the significant safety and tolerability concerns with dopamine agonists and only mild efficacy of MAO-B inhibitors. Recently, P2B001, a novel drug formulation combining once-daily, extended-release, low dosages of the dopamine agonist pramipexole and the MAO-B inhibitor rasagiline (0.6 mg and 0.75 mg respectively), has entered clinical development. In this article, the authors review the preclinical and current clinical data on P2B001 and its components. The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa. [ABSTRACT FROM AUTHOR]