Factor Stewart A
Department of Neurology, Emory University School of Medicine, 1841 Clifton Road NE, Atlanta, Georgia 30329, USA.
Neurotherapeutics. 2008 Apr;5(2):164-80. doi: 10.1016/j.nurt.2007.12.001.
Symptomatic medical therapies for Parkinson's disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended. Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.
帕金森病(PD)的症状性药物治疗具有疾病修饰作用,可改善日常功能、生活质量并延长生存期。40年来,这些治疗主要是多巴胺能治疗,目前包括多巴胺(DA)前体左旋多巴(LD)、DA激动剂、儿茶酚-O-甲基转移酶(COMT)抑制剂和单胺氧化酶(MAO)抑制剂。所有这些药物类别的作用都在演变,自21世纪初以来发生了重大变化。本文综述了这些药物类别的当前文献,重点关注疗效和在治疗方案中的地位。左旋多巴不再被认为有毒性,因此,早期使用不仅合适而且是推荐的。麦角激动剂已不再使用,以贴片形式或皮下注射给药的新药物已获批准。具有显著疗效的COMT抑制剂托卡朋已重新上市,两种新的MAO抑制剂已获批准。本文还讨论了一些特定的安全问题,包括与左旋多巴相关的黑色素瘤发病率;病理性赌博与DA激动剂;托卡朋的肝毒性;以及MAO B抑制剂与酪胺或所谓的奶酪反应。文章最后讨论了未来的方向和正在研发的新药。