COMT抑制剂在帕金森病中的临床药理学、治疗用途和潜力。

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COMT抑制剂在帕金森病中的临床药理学、治疗用途和潜力。

药物。2000 Jun;59(6):1233-50。

PubMed ID

10882160 (PubMed视图

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摘要

当外周脱羧被卡比多巴或苯拉齐特阻断时，左旋多巴的主要代谢途径是儿茶酚- o -甲基转移酶(COMT)的o -甲基化。安他卡酮和托尔卡酮是新型有效、选择性和可逆的硝基儿茶酚型COMT抑制剂。动物研究表明，安他卡酮主要具有外周效应，而托尔卡酮也抑制大脑中的o -甲基化。在人类志愿者中，安他卡彭和托卡彭均剂量依赖性地抑制红细胞COMT活性，提高左旋多巴的生物利用度并减少左旋多巴的消除，并抑制3- o -甲基多巴(3-OMD)的形成。安他卡彭与每一预定剂量的左旋多巴一起服用，而托尔卡彭每天服用3次。这些药物的不同给药方案是基于它们不同的药代动力学和药效学特征。安他卡彭和托尔卡彭均可增强和延长左旋多巴对晚期波动性帕金森病患者的治疗效果。它们延长了左旋多巴效应的持续时间。临床研究表明，他们每天平均增加1至3小时的ON时间，改善日常生活活动，并允许每日左旋多巴剂量减少。相应地，他们大大减少了每天的OFF时间。 No comparative studies between entacapone and tolcapone have been performed. Tolcapone also appears to have a beneficial effect in patients with nonfluctuating Parkinson's disease. The main adverse effects of the COMT inhibitors are related to their dopaminergic and gastrointestinal effects. Enhancement of dopaminergic activity may cause an initial worsening of levodopa-induced adverse effects, such as dyskinesia, nausea, vomiting, orthostatic hypotension, sleep disorders and hallucinations. Levodopa dose adjustment is recommended to avoid these events. Tolcapone is associated with diarrhoea in about 16 to 18% of patients and entacapone in less than 10% of patients. Diarrhoea has led to discontinuation in 5 to 6% of patients treated with tolcapone and in 2.5% of those treated with entacapone. Urine discoloration to dark yellow or orange is related to the colour of COMT inhibitors and their metabolites. Elevated liver transaminase levels are reported in 1 to 3% of patients treated with tolcapone but very rarely, if at all, in patients treated with entacapone. The descriptions of acute, fatal fulminant hepatitis and potentially fatal neurological reactions, such as neuroleptic malignant syndrome and rhabdomyolysis, in association with tolcapone led to the suspension of its marketing authorisation in the European Community and Canada. In many other countries, the use of tolcapone is restricted to patients who are not responding satisfactorily to other therapies. Regular monitoring of liver enzymes is required if tolcapone is used. No such adverse reactions have so far been described for entacapone and no laboratory monitoring has been proposed. COMT inhibitors added to levodopa therapy are beneficial, particularly in patients with fluctuating disease. They may be combined with other antiparkinsonian drugs, such as dopamine agonists, selegiline and anticholinergics without adverse interactions. They provide a new treatment possibility in patients with Parkinson's disease who have problems with their present levodopa therapy.

引用本文的药物库数据

药物

Tolcapone

Entacapone

药物靶点

药物	目标	种类	生物	药理作用	行动
Entacapone	儿茶酚O-methyltransferase	蛋白质	人类	是的	抑制剂	细节
Tolcapone	儿茶酚O-methyltransferase	蛋白质	人类	是的	抑制剂	细节