临床药理学治疗使用和转移酶抑制剂在帕金森病的潜力。

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Kaakkola年代

临床药理学治疗使用和转移酶抑制剂在帕金森病的潜力。

药。2000年6月,59 (6):1233 - 50。

PubMed ID

10882160 (在PubMed

]

文摘

当外围脱酸被卡比多巴或benserazide,左旋多巴的主要代谢途径由catechol-O-methyltransferase O-methylation (COMT的)。Entacapone和tolcapone新的强有力的、有选择性的、可逆的nitrocatechol-type COMT的抑制剂。动物研究已经证明,entacapone主要有边缘效应而tolcapone还能抑制大脑中O-methylation。在人类志愿者,entacapone和tolcapone剂量依赖性抑制红细胞COMT的活动,提高生物利用度,减少左旋多巴的消除和抑制3-O-methyldopa的形成(3-OMD)。Entacapone管理每预定剂量左旋多巴而tolcapone管理每日3次。这些代理的不同管理方案是基于他们不同的药代动力学和药效学资料。entacapone和tolcapone增强和延长晚期患者的左旋多巴的疗效和波动的帕金森病。他们延长左旋多巴的时间效应。临床研究表明,他们增加每日平均1到3小时,改善日常生活的活动,允许每日左旋多巴用量减少。相应地,他们大大减少每日的时间。 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.

DrugBank数据引用了这篇文章

药物

Tolcapone

Entacapone

药物靶点

药物	目标	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