Catechol‐O‐methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients
Catechol‐O‐methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients
复制标题
儿茶酚-O-甲基转移酶抑制剂托卡朋可延长帕金森病患者的左旋多巴/卡比多巴作用
作者：
J. Roberts;G. Corá;D. Bravi;M. Amantea;M. Mouradian;T. Chase
帕金森氏病（PD）的左旋多巴治疗中经常会出现这种现象。当突触内多巴胺浓度开始反映标准给药方案中左旋多巴可用性的波动时，出现这些反应波动。因此，延长左旋多巴和多巴胺生物半衰期的药物应该是有益的。我们给药左旋多巴卡比多巴与单次口服剂量的托卡朋（Ro 40-7592），儿茶酚-O-甲基转移酶的抑制剂，在控制条件下，10例PD患者的磨损现象。在50 ~ 400 mg的剂量范围内，托卡朋使左旋多巴和卡比多巴的抗帕金森反应延长约67%（p < 0.05）。左旋多巴对帕金森症状的峰值效应或运动障碍的严重程度没有显著变化。未发生剂量限制性不良反应。因此，预期托卡朋每日多次给药可安全地减少与左旋多巴/卡比多巴治疗相关的磨损现象。
The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopdcarbidopa in combination with single oral doses of tolcapone (Ro 40–7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopdcarbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safely reduce the wearing-off phenomenon associated with levodopdcarbidopa therapy.
Sinemet CR4 和标准 Sinemet 25/100 在帕金森病和运动能力波动患者中的双盲交叉比较。
DOI：
10.1136/jnnp.52.2.207
发表时间：
1989
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Cedarbaum,JM;Hoey,M;McDowell,FH
通讯作者：
McDowell,FH