左旋多巴
医学
多巴胺
多巴胺能
不利影响
多巴胺受体D3
兴奋剂
帕金森病
部分激动剂
疾病
神经科学
药理学
内科学
心理学
受体
作者
Erwan Bézard,David Gray,Rouba Kozak,Matthew Leoni,Cari Combs,Sridhar Duvvuri
出处
期刊:Cns & Neurological Disorders-drug Targets
[Bentham Science]
日期:2023-03-31
卷期号:23 (4): 476-487
被引量:6
标识
DOI:10.2174/1871527322666230331121028
摘要
Abstract: Currently, available therapeutics for the treatment of Parkinson’s disease (PD) fail to provide sustained and predictable relief from motor symptoms without significant risk of adverse events (AEs). While dopaminergic agents, particularly levodopa, may initially provide strong motor control, this efficacy can vary with disease progression. Patients may suffer from motor fluctuations, including sudden and unpredictable drop-offs in efficacy. Dopamine agonists (DAs) are often prescribed during early-stage PD with the expectation they will delay the development of levodopa-associated complications, but currently available DAs are less effective than levodopa for the treatment of motor symptoms. Furthermore, both levodopa and DAs are associated with a significant risk of AEs, many of which can be linked to strong, repeated stimulation of D2/D3 dopamine receptors. Targeting D1/D5 dopamine receptors has been hypothesized to produce strong motor benefits with a reduced risk of D2/D3-related AEs, but the development of D1-selective agonists has been previously hindered by intolerable cardiovascular AEs and poor pharmacokinetic properties. There is therefore an unmet need in PD treatment for therapeutics that provide sustained and predictable efficacy, with strong relief from motor symptoms and reduced risk of AEs. Partial agonism at D1/D5 has shown promise for providing relief from motor symptoms, potentially without the AEs associated with D2/D3-selective DAs and full D1/D5-selective DAs. Tavapadon is a novel oral partial agonist that is highly selective at D1/D5 receptors and could meet these criteria. This review summarizes currently available evidence of tavapadon’s therapeutic potential for the treatment of early through advanced PD.
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