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“美多芭”与左旋司来吉兰联合治疗帕金森病的意义。一项长期研究。

Implications of combined treatment with 'Madopar' and L-deprenil in Parkinson's disease. A long-term study.

作者信息

Birkmayer W, Riederer P, Ambrozi L, Youdim M B

出版信息

Lancet. 1977 Feb 26;1(8009):439-43. doi: 10.1016/s0140-6736(77)91940-7.

Abstract

In a clinical trial the effect of L-deprenil, a selective irreversible inhibitor of monoamine oxidase (M.A.O.) "type B" in potentiating the anti-kinetic properties of levodopa has been investigated in 223 patients. Both drugs were given orally, levodopa as 'Madopar' (levodopa plus the peripherally acting decarboxylase inhibitor, benserazide) 250 mg three times daily and L-deprenil 5 mg once or twice daily. The addition of L-deprenil to madopar therapy resulted in a statistically significant (P less than 0-01-0-001) reduction in patients' functional disability on average within 60 min after a single oral dose and lasting for 1 to 3 days. Dyskinesia occurred in 16 patients, psychosis in 14, orthostatic hypotension in 5, and nausea in 8. Reduction of the L-deprenil dose to 5 mg in these patients eliminated some of the side-effects. Two-thirds of the patients with side-effects had suffered from parkinsonism for between 7 and 15 years. 14% of the patients failed to respond to madopar-deprenil therapy. It is suggested that L-deprenil may act through inhibition of brain M.A.O. as well as by a psychostimulant effect similar to that of amphetamine which occurs through the release of dopamine. Both mechanisms would make more dopamine available at dopamine receptor sites.

摘要

在一项临床试验中,对223例患者研究了左旋司来吉兰(一种选择性不可逆单胺氧化酶“B型”抑制剂)增强左旋多巴抗运动不能特性的效果。两种药物均口服给药,左旋多巴以“美多芭”(左旋多巴加外周作用的脱羧酶抑制剂苄丝肼)每日3次、每次250mg给药,左旋司来吉兰每日1次或2次、每次5mg给药。在美多芭治疗中加用左旋司来吉兰后,单次口服给药后平均60分钟内患者的功能残疾有统计学显著降低(P小于0.01至0.001),并持续1至3天。16例患者出现运动障碍,14例出现精神病,5例出现体位性低血压,8例出现恶心。在这些患者中将左旋司来吉兰剂量减至5mg消除了一些副作用。三分之二有副作用的患者患帕金森病已有7至15年。14%的患者对美多芭 - 司来吉兰治疗无反应。提示左旋司来吉兰可能通过抑制脑内单胺氧化酶以及通过类似于苯丙胺的精神兴奋作用(通过释放多巴胺产生)发挥作用。两种机制都会使更多多巴胺在多巴胺受体部位可用。

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