کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2563761 | 1127563 | 2010 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
From the cell to the clinic: A comparative review of the partial D2/D3 receptor agonist and α2-adrenoceptor antagonist, piribedil, in the treatment of Parkinson's disease
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کلمات کلیدی
COMTG-protein receptor kinaseGRKWCSTα2-adrenoceptorPramipexoleadrenoceptorUPDRSGIRKMAOSTNNBMGPCRMPTPFCxGSK-3βAntiparkinsonERKPergolideBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز G-protein coupled receptor - G-پروتئین همراه گیرندهl-3,4-dihydroxyphenylalanine - L-3،4-دی هیدروکسی فنیل آلانینl-DOPA - L-DOPA[35S]GTPγS - [35S] GTPγSACh - آهAkt - آکتAcetylcholine - استیل کولینγ-aminobutyric acid - اسید γ-آمینوبوتیریکParkinson's disease - بیماری پارکینسونWisconsin Card Sorting Test - تست مرتب سازی کارت ویسکانسینfMRI - تصویرسازی تشدید مغناطیسی کارکردیfunctional magnetic resonance imaging - تصویرسازی تشدید مغناطیسی کارکردیDopamine - دوپامینRopinirole - روپینیرولbrain derived neurotrophic factor - عامل مغز استخوان مغز استخوان استfrontal cortex - قشر جلوییlocus coeruleus - لوکوس سیرولئوسUnified Parkinson's Disease Rating Scale - مقیاس درجه بندی بیماری بیماری پارکینسون متحدmonoamine oxidase - مونوآمین اکسیدازها noradrenaline - نورآدرنالین nucleus basalis of Meynert - هسته پایه MeynertSubthalamic nucleus - هسته ی زیرهالامیکatypical kinase - کیناز آتیپیکextracellular regulated kinase - کیناز تنظیم شده خارج سلولیGABA - گاباGlycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3βD2 receptor - گیرنده D2D3 receptor - گیرنده D3
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: From the cell to the clinic: A comparative review of the partial D2/D3 receptor agonist and α2-adrenoceptor antagonist, piribedil, in the treatment of Parkinson's disease From the cell to the clinic: A comparative review of the partial D2/D3 receptor agonist and α2-adrenoceptor antagonist, piribedil, in the treatment of Parkinson's disease](/preview/png/2563761.png)
چکیده انگلیسی
Though l-3,4-dihydroxyphenylalanine (L-DOPA) is universally employed for alleviation of motor dysfunction in Parkinson's disease (PD), it is poorly-effective against co-morbid symptoms like cognitive impairment and depression. Further, it elicits dyskinesia, its pharmacokinetics are highly variable, and efficacy wanes upon long-term administration. Accordingly, “dopaminergic agonists” are increasingly employed both as adjuncts to L-DOPA and as monotherapy. While all recognize dopamine D2 receptors, they display contrasting patterns of interaction with other classes of monoaminergic receptor. For example, pramipexole and ropinirole are high efficacy agonists at D2 and D3 receptors, while pergolide recognizes D1, D2 and D3 receptors and a broad suite of serotonergic receptors. Interestingly, several antiparkinson drugs display modest efficacy at D2 receptors. Of these, piribedil displays the unique cellular signature of: 1), signal-specific partial agonist actions at dopamine D2and D3 receptors; 2), antagonist properties at α2-adrenoceptors and 3), minimal interaction with serotonergic receptors. Dopamine-deprived striatal D2 receptors are supersensitive in PD, so partial agonism is sufficient for relief of motor dysfunction while limiting undesirable effects due to “over-dosage” of “normosensitive” D2 receptors elsewhere. Further, α2-adrenoceptor antagonism reinforces adrenergic, dopaminergic and cholinergic transmission to favourably influence motor function, cognition, mood and the integrity of dopaminergic neurones. In reviewing the above issues, the present paper focuses on the distinctive cellular, preclinical and therapeutic profile of piribedil, comparisons to pramipexole, ropinirole and pergolide, and the core triad of symptoms that characterises PD-motor dysfunction, depressed mood and cognitive impairment. The article concludes by highlighting perspectives for clarifying the mechanisms of action of piribedil and other antiparkinson agents, and for optimizing their clinical exploitation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 128, Issue 2, November 2010, Pages 229-273
Journal: Pharmacology & Therapeutics - Volume 128, Issue 2, November 2010, Pages 229-273
نویسندگان
Mark J. Millan,