Sedehizadeh Saam, Keogh Michael, Maddison Paul
Department of Clinical Neurology, Queen's Medical Centre, Nottingham, UK.
Clin Neuropharmacol. 2012 Jul-Aug;35(4):191-200. doi: 10.1097/WNF.0b013e31825a68c5.
Aminopyridines are members of a family of monoamino and diamino derivatives of pyridine, and their principal mechanism of action is dose-dependent blockade of voltage-gated potassium channels, in particular, fast voltage-gated potassium channels. To date, only 2 main broad-spectrum potassium channel blockers, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), have been used as investigational new drugs in various neurological diseases. More recently, licensed versions of these compounds including dalfampridine extended release (Fampyra, Biogen Idec) for the improvement of walking in adult patients with multiple sclerosis, and amifampridine (Firdapse, Biomarin Europe Ltd) for the treatment of Lambert-Eaton myasthenic syndrome have been released, and the costs associated with using these new products highlights the importance of evaluating the clinically meaningful treatment effects of these drugs.The current review summarizes the evidence of aminopyridine use in neurological conditions and in particular presents a systematic review of all randomized trials of 3,4-DAP in Lambert-Eaton myasthenic syndrome to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points.
氨基吡啶是吡啶单氨基和二氨基衍生物家族的成员，其主要作用机制是对电压门控钾通道进行剂量依赖性阻断，尤其是快速电压门控钾通道。迄今为止，仅有两种主要的广谱钾通道阻滞剂，即4-氨基吡啶（4-AP）和3,4-二氨基吡啶（3,4-DAP），被用作多种神经疾病的研究性新药。最近，这些化合物的获批版本已上市，包括用于改善成年多发性硬化症患者步行能力的缓释达氟吡啶（Fampyra，百健艾迪公司），以及用于治疗兰伯特-伊顿肌无力综合征的阿米吡啶（Firdapse，欧洲生物马林公司），使用这些新产品的相关成本凸显了评估这些药物临床意义上治疗效果的重要性。本综述总结了氨基吡啶在神经疾病中应用的证据，尤其对3,4-DAP治疗兰伯特-伊顿肌无力综合征的所有随机试验进行了系统综述，以通过对临床和电生理终点进行荟萃分析来确定该治疗方法的疗效。
