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pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

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Neural Regeneration Research 2022年第2期17卷 450-458页

作者： Carlos Pereira Martins Rodrigo Sebben Paes Gabriela Mantovani Baldasso Eduarda Gomes Ferrarini Rahisa Scussel Rubya Pereira Zaccaron Ricardo Andrez Machado-de-Avila Paulo Cesar Lock Silveira Rafael Cypriano Dutra Laboratory of Autoimmunity and Immunopharmacology Department of Health SciencesCampus AraranguaUniversidade Federal de Santa CatarinaAraranguáSCBrazil Post-Graduate Program of Neuroscience Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisSCBrazil Laboratory of Experimental Physiopathology Program of Postgraduate in Science of HealthUniversidade do Extremo Sul CatarinenseCriciumaSCBrazil

Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.

关键词： dopamine dopaminergic system fibromyalgia hyperalgesia pain pramipexole reserpine

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pramipexole in Treatment Resistant Depression: A Case Review

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Pharmacology & Pharmacy 2023年第7期14卷 223-227页

作者： Nada Abdallah Jeffrey Kahn Weill Cornell Medicine New York NY USA Department of Psychiatry Weill Cornell Medicine New York NY USA

pramipexole is a dopamine agonist used in the treatment of Parkinson’s disease and Restless legs syndrome. Although off-label, the use of pramipexole as an adjunct therapy in treatment resistant depression has recently been documented in the literature with promising results. We present a 75-year-old male with MDD who has failed trials of SSRIs, SNRIs, TCAs, SGA, TMS, Ketamine, and ECT who was initiated on pramipexole. We discuss, based on existing literature, the probability of a favorable long-term response to pramipexole and the potential side effects for our patient. We also highlight the need for future studies designed to test the efficacy of pramipexole in geriatric patients with TRD.

关键词： pramipexole Treatment Resistant Depression Augmentation Dopamine Agonism Geriatric Psychiatry

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Self-Reported Adherence after Overnight Switching from Immediate- to Extended-Release pramipexole in Parkinson’s Disease

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Advances in Parkinson's Disease 2015年第1期4卷 13-19页

作者： Mutsumi Iijima Mikio Osawa Kenji Maruyama Shinichiro Uchiyama Kazuo Kitagawa Department of Neurology Tokyo Women’s Medical University School of Medicine Tokyo Japan

Background: Drug adherence decreased in patients with Parkinson’ s disease (PD) because of taking many different types of drugs. We evaluated drug adherence after switching from immediate-release (IR) to once-daily extended-release (ER) pramipexole (PPX) in PD. Methods: This study included 35 PD patients (20 men, 15 women);10 were taking oral PPX alone, and 25 were also using another anti-PD drug. PPX-IR was switched overnight to PPX-ER without gradual tapering. One month after switching, improvement in timing adherence and reduction in medication burden were evaluated by a questionnaire using a visual analog scale (VAS) (0: No change;10: Better). Motor function was assessed using part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: The VAS score for improvement in timing adherence was 8.1 ± 0.5 (mean ± standard error), and that for reduction in medication burden was 7.3 ± 0.6. There was a significant negative correlation (ρ = -0.43, p = 0.01) between the VAS score and number of types of medications. The UPDRS part III score improved significantly after switching

关键词： Parkinson’s Disease Timing Adherence pramipexole Extended-Release Immediate-Release Motor Function

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Alpha-Dihydroergocryptine vs. pramipexole as Adjunct Symptomatic Treatment of Idiopathic Parkinson’s

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Advances in Parkinson's Disease 2015年第1期4卷 1-8页

作者： Ulises Rodríguez Ortiz Daniel San- Juan Francesco Scarci Movement Disorders Clinic and Neurophysiology Department Instituto Nacional de Neurología y Neurocirugía Mexico City Mexico Scientific Department Polichem S.A. Lugano Switzerland

A randomized, double blind, and active reference-controlled study was carried out among 116 patients suffering from idiopathic Parkinson’s disease (PD). The aim of the study was to compare the safety and efficacy of alpha-dihydroergocryptine (DHEC) vs. pramipexole (PRAM) as an adjunct symptomatic therapy to levodopa in PD patients. The motor symptoms, assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) III subscale, was identified as efficacy target. Fifty-six patients were randomized to DHEC and 60 to PRAM. Patients included were under constant levodopa dose for at least 3 months before entering the study, with baseline UPDRS III ≥14. They underwent a 16-week treatment. Out of the 116 included patients, 85 (39 in DHEC group and 46 in PRAM group, respectively) completed the study protocol. In DHEC group, UPDRS III decreased by 24.2% from baseline at week 10 and by 28.1% at week 16. In PRAM group, UPDRS III decreased by 27.1% from baseline at week 10 and by 29.2% at week 16. The data were highly significant

关键词： Adjunct Symptomatic Therapy Alpha-Dihydroergocryptine pramipexole Idiopathic Parkinson’s Disease Motor Complications UPDRS

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Efficacy of pramipexole for Treatment of Apathy in Parkinson’s Disease

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International Journal of Clinical Medicine 2014年第15期5卷 885-889页

作者： Hiroaki Oguro Katsuhiko Kadota Masaki Ishihara Kazunori Okada Shuhei Yamaguchi Department of Neurology Faculty of Medicine Shimane University Shimane Japan Department of Neurology Ohda Silver Clinic Shimane Japan Department of Neurology Tokyo Metropolitan Health and Medical Treatment Corporation Toshima Hospital Tokyo Japan

Background: Apathy occurs frequently in patients with Parkinson’s disease (PD), and has a negative impact on activities of daily living through loss of motivation. pramipexole (PPX), which shows preferential affinity for D3 dopamine receptor in the mesolimbic system, is thought to influence mood and motivation. Therefore, we conducted an open-label case-control study to examine the effect of PPX on apathy in PD. Methods: We studied 36 PD patients (mean age, 70.4 ± 8.1 years), who had been treated only with L-DOPA. PPX was added to L-DOPA treatment in 24 patients (PPX group) and other 12 patients continued with L-DOPA alone (non-PPX group). The study period was 8 weeks. Apathy was assessed using the revised apathy scale for Japanese. Motor function was assessed with part III of the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: Seventeen of 36 patients (47%) were diagnosed as having apathy. In the PPX group, apathy scale significantly improved from 17.3 to 13.8 at week 8 (p < 0.05). Motor function also improved significantly from 16.1 to 7.6 at week 8 (p < 0.0001). In the non-PPX group, apathy scale and UPDRS both showed no change during the study period. There was no correlation between changes in apathy scale and UPDRS in either the PPX or non-PPX group. Conclusion: PPX may be effective for treating apathy as well as motor dysfunction in PD.

关键词： pramipexole Apathy Parkinson’s disease Depression UPDRS

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Pathological Gambling after Administration of pramipexole

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Case Reports in Clinical Medicine 2018年第5期7卷 349-351页

作者： Konstantinos Kontoangelos Marina Ecomomou Charalambos Papageorgiou 1^st Department of Psychiatry Medical School National & Kapodistrian University of Athens Eginition Hospital Athens Greece University Mental Health Research Institute Athens Greece

Parkinson’s disease is a common condition usually treated by dopaminergic agents and many behavioral abnormalities such as impulse control disorders (ICD) are connected with that usage. Pathological gambling, a form of ICD includes is a clinical condition that disrupts personal, family and occupational activity. pramipexole a D2 AND D3 agonist may be associated with pathological gambling. We present a case of 74-year-old male patient who was diagnosed with Parkinson’s disease (PD). His doctor advised him to take pramipexole 0.18 mg/p.o./day. A month after the onset of treatment he manifested a behavior of pathological gambling. After the discontinuation of the drug all this behavior was interrupted.

关键词： pramipexole Pathological Gambling Side Effects Parkinson Disease

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A DOPAMINE AGONIST,pramipexole,AND COGNITIVE FUNCTIONS IN PARKINSON’S DISEASE

A DOPAMINE AGONIST,PRAMIPEXOLE,AND COGNITIVE FUNCTIONS IN PA...

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第十五届国际药理学大会

作者： Maja Relja Nataa Klepac and Vladimir Miletic Department of Neurology Medical SchoolUniversity of Zagreb10 000ZagrebCroatia Department of Neurology Medical SchoolUniversity of Zagreb10 000ZagrebCroatia

＜正＞ PD has long been conceived to be mainly a motor disorder. In the last few decades it has been increasingly more recognized that many patients with PD will experience cognitive decline in the course of their illness. Dopamine agonists have shown beneficial therapeutic effects on motor symptoms in PD. but their influence on cognitive functions is still controversial. The aim of this study is to evaluate the influence of the dopamine agonist pramipexole on cognitive functions in PD patients already treated with *** cognitive performance of 55 non - demented idiopathic Parkinson’s disease （PD） patients treated with levodopa alone or receiving dopamine agonist pramipexole as add on therapy to levodopa was evaluated in the present study during six month of treatment. Neuropsychological tests were administered two times. In the first assessment to differentiate test sensitive to cognitive changes typical for PD control group was also assessed. After six months of treatment PD patients were retested only with tests that differentiate them from control group. Compared to controls PD patients showed inferior performance on Stroop Interference test. Trail Making test,letter fluency and Hooper Visual Organization test. No statistically significant differences between two groups and first and second neuropsychological assessment was found. In conclusion: present findings indicate that pramipexole as add - on therapy to levodopa is safe in non - demented PD patients in terms of the effect on cognitive performance.

关键词： Parkinson’ s disease cognitive functions dopamine agonists pramipexole

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pramipexole和左旋多巴在帕金森病初始治疗中的应用—随机对照试验

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美国医学会杂志（中文版） 2001年第3期20卷 107-114页

作者：黄觉斌

背景：pramipexole和左旋多巴均能缓解早期帕金森病（Parkinson Disease，PD）的运动症状，但是对采用pramipexole或左旋多巴进行多巴胺能类药物初始治疗后的长期结果，尚无对照研究对其加以比较。目的：对采用pramipexole与左旋多巴... 详细信息

背景：pramipexole和左旋多巴均能缓解早期帕金森病（Parkinson Disease，PD）的运动症状，但是对采用pramipexole或左旋多巴进行多巴胺能类药物初始治疗后的长期结果，尚无对照研究对其加以比较。目的：对采用pramipexole与左旋多巴作为早期PD初始治疗药物发生多巴胺能运动并发症的危险性进行比较。设计：多中心、平行组、双盲、随机对照试验。地点：美国和加拿大22个运动障碍疾病门诊。患者：301例有明显运动障碍需要接受多巴胺能药物治疗的早期PD患者，在1996年10月至1997年8月入组。治疗方法：受试者随机分为pramipexole组和左旋多巴组。pramipexole组服用pramipexole 0.5 mg，每日3次，同时服用左旋多巴安慰剂（n=151）；左旋多巴组服用卡比多巴/左旋多巴，25/100 mg，每日3次，同时服用pramipexole安慰剂（n=150）。运动障碍改善不满意的患者，在最初10周内剂量可以逐渐增加。从第11周到第23.5个月，研究者可额外加用左旋多巴以便治疗一直存在或新出现的功能障碍。主要观察指标：第一次出现下列任何一种并发症的时间：剂末效应（wearing off）、异动症、或开关样运动波动；基线以及随访时统一帕金森病评分量表（Unified Parkinson's Disease Rating Scale，UPDRS）得分变化；在一个有82例受试者的亚组中，对基线与23.5个月时用单光子发射计算机断层显像技术观察到的多巴胺转运体特异性和非置换性纹状体123碘2-β-羧甲基-3-β-（4-碘酚）烷（β-CIT）摄取的比率进行了评估。结果：采用pramipexole初始治疗的患者发生剂末效应、异动症或开关样运动波动的危险性显著低于左旋多巴组（28％:51％；风险比［hazard ratio］，0.45；95％可信区间［CI］，0.30～0.66；P＜0.001）。从基线到23.5个月UPDRS总积分的平均改善值左旋多巴组大于pramipexole组（9.2分:4.5分；P＜0.001）。嗜睡在pramipexole治疗组比左旋多巴治疗组更常见（32.4%:17.3%；P=0.003），这种差异出现在剂量递增阶段。在亚组研究中，用pramipexole进行初始治疗的患者（n＝39）纹状体β-CIT摄取下降的平均（SD）值为20.0%（14.2%），而左旋多巴初始治疗的患者（n=39）则为4.8%（14.4%）（P=0.15）。结论：与接受左旋多巴初始治疗的患者比较，接受pramipexole初始治疗的PD患者较少发生多巴胺能运动并发症。排除两组额外添加左旋多巴治疗的因素，左旋多巴治疗组UPDRS总分的改善比pramipexole组明显。

关键词：帕金森病初始治疗 pramipexole 左旋多巴

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