Bourque Mélanie, Morissette Marc, Bortolato Marco, Frau Roberto, Carta Manolo, Di Paolo Thérèse
Centre de Recherche du CHU de Québec, Québec, QC, Canada.
Department of Cellular and Systems Pharmacology, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Mov Disord. 2025 Sep;40(9):1996-2001. doi: 10.1002/mds.30280. Epub 2025 Jul 5.
Pregnenolone is the first neurosteroid synthesized from cholesterol in the brain. Previous studies showed that it reduces the development of levodopa (L-dopa)-induced dyskinesias (LIDs) in rat models of Parkinson's disease (PD).
To examine whether pregnenolone mitigates established LIDs in a non-human primate model.
Ovariectomized female macaques, modeling the postmenopausal hormonal status of most women with PD, were lesioned with MPTP and treated with L-dopa to induce LIDs. Pregnenolone was administered subcutaneously (SC) at 6 or 18 mg/kg or orally (36 mg/kg).
Pregnenolone reduced established LIDs in MPTP-lesioned monkeys while preserving L-dopa's antiparkinsonian effects. The antidyskinetic effect was dose-dependent, with the greatest reduction observed at 18 mg/kg SC, followed by 6 mg/kg SC, and a lesser effect at 36 mg/kg orally, likely due to first-pass metabolism.
Pregnenolone reduces established LIDs in parkinsonian monkeys and may represent a safe, novel therapeutic candidate for dyskinesia treatment in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
孕烯醇酮是大脑中由胆固醇合成的第一种神经甾体。先前的研究表明，它能减少帕金森病（PD）大鼠模型中左旋多巴（L -多巴）诱导的异动症（LIDs）的发生。
研究孕烯醇酮是否能减轻非人类灵长类动物模型中已形成的LIDs。
对去卵巢的雌性猕猴进行MPTP损伤，模拟大多数患PD的绝经后女性的激素状态，并用L -多巴治疗以诱导LIDs。孕烯醇酮以6或18mg/kg的剂量皮下注射（SC）或口服（36mg/kg）。
孕烯醇酮可减轻MPTP损伤猴子中已形成的LIDs，同时保留L -多巴的抗帕金森病作用。抗异动症作用呈剂量依赖性，在18mg/kg SC时观察到最大程度的减轻，其次是6mg/kg SC，口服36mg/kg时作用较小，这可能是由于首过代谢。
孕烯醇酮可减轻帕金森病猴子中已形成的LIDs，可能是治疗PD异动症的一种安全、新型的候选治疗药物。© 2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
