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Piribedil: Antiparkinsonian Properties and Potential Clinical Utility in Dopaminergic Disorders

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Piribedil is a relatively unknown non-ergot dopamine agonist that has been in clinical use for over 3 decades for the symptomatic management of Parkinson's disease (PD). Piribedil is currently not approved for therapeutic use in the United States. It has unique pharmacological and pharmacokinetic attributes with a profile that is unlike many direct dopamine agonists. In addition to proven motor effects in PD, nonclinical and clinical evidence over the last few years indicate that piribedil may also exert beneficial non-motor effects such as in mild cognitive impairment and frontal cognitive dysfunctions prevalent in PD patients. This review presents the pharmaceutics, pharmacological pleiotropy, and clinical properties of piribedil with a focus on its utility in the therapy of motor and non-motor symptoms in PD and related dopaminergic disorders. The varied pharmacological, behavioral, and clinical properties of piribedil are related to current knowledge on its multifunctional pharmacology. Properties of piribedil that may differentiate it from other dopamine direct agonists are noted. As a partial agonist of dopamine D2 and D3 receptors with functional α2 adrenolytic activity, piribedil may be an alternative to the inherent anti-akinetic (beneficial) and dyskinetic (unwanted) effects of some dopamine replacement therapies. The activation of limbic dopamine receptors by piribedil and stimulation of acetylcholine release in the frontal cortex provide a basis for improving mood and cognitive disturbances. Additionally, α2 antagonism and weak 5-HT1A agonism may provide beneficial effects on dyskinesias, neuropsychiatric symptoms in PD, neurotrophic effects, and reduced sedation. The adverse effects of piribedil generally mirror its monoaminergic activity and include nausea, vomiting, abnormal sleep events, and psychiatric effects such as psychosis and compulsive disorders. While the therapeutic potential of piribedil may yet to be fully realized, investigations of its safety and toxicology under current standards of drug development are warranted before exposure to new patient populations.





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Keywords: Adrenergic antagonist; CNS disease; N-oxidation; Parkinson's disease; absorption; acetylcholinesterase inhibitors (AChEi); alopecia; anxiety; attention; axial symptoms; basal ganglia; bioavailability; bitter taste; brains; catechol; cognitive dysfunction; colon; crystalline; dementia; depression; dopamine agonist; dopamine receptors; dorsal raphe nucleus (DRN); dose; dose-dependent receptor; drug exposures; drug repositioning; dysfunction; dyskinesias; dystonia; elimination; executive functions; frontotemporal dementia; half-life; hypotension; insomnia; isoenzymes; levodopa; locus coeruleus; nausea; neurodegenerative disorder; neurons; odorless; oral; peripheral edema; pharmacokinetics; plasma; plasma levels; properties; psychosis; renal excretion; schizophrenia; smoking cessation; somnolence; striatal dopamine; sublingual; suboptimal dosing; substantia nigra pars compacta; tremor; urine

Document Type: Research Article

Publication date: 01 February 2011

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  • Current Drug Therapy publishes frontier reviews on all the latest advances in drug therapy. The journal's aim is to publish the highest quality review articles in the field. Topics covered include: new and existing drugs, therapies and medical devices.

    The journal is essential reading for all researchers and clinicians involved in drug therapy.
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