Plosker Greg L, Scott Lesley J
Adis International Limited, Auckland, New Zealand.
CNS Drugs. 2006;20(7):601-8; discussion 609-10. doi: 10.2165/00023210-200620070-00005.
Retigabine has anticonvulsant properties that appear to be primarily mediated by opening neuronal voltage-gated potassium channels. This action has been shown in neuronal KCNQ2/3 and KCNQ3/5 potassium channels. In addition to this unique action, retigabine also potentiates GABA-evoked currents in cortical neurons at high concentrations. When used as adjunctive therapy in patients with partial seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was associated with significant linear dose-dependent reductions in monthly seizure frequency compared with placebo in a large 16-week randomised phase II trial. Median monthly seizure frequency decreased from baseline by up to 35% among patients in the retigabine treatment arms compared with 13% in the placebo group. Retigabine 1200 mg/day was also significantly more effective than retigabine 600 mg/day. Responder rates, defined as the proportion of patients with > or = 50% reduction in seizure frequency, were significantly higher among patients in the retigabine 900 and 1200 mg/day groups than in those who received placebo. CNS-related adverse events were the most commonly reported treatment-emergent adverse events associated with retigabine in clinical trials. Across all three retigabine groups in the large phase II trial, somnolence (20.3%), dizziness (14.6%), confusion (12.3%) and speech disorder (11.3%) were the most frequent CNS-related adverse events.
瑞替加滨具有抗惊厥特性,其作用似乎主要通过打开神经元电压门控钾通道介导。这种作用已在神经元KCNQ2/3和KCNQ3/5钾通道中得到证实。除了这种独特作用外,瑞替加滨在高浓度时还能增强皮质神经元中γ-氨基丁酸(GABA)诱发的电流。在一项为期16周的大型随机II期试验中,当瑞替加滨作为部分性癫痫患者的辅助治疗药物使用时,与安慰剂相比,600 - 1200毫克/天(200 - 400毫克,每日三次)的瑞替加滨与每月癫痫发作频率呈显著的线性剂量依赖性降低相关。与安慰剂组13%的降低率相比,瑞替加滨治疗组患者的每月癫痫发作频率中位数从基线水平降低了高达35%。1200毫克/天的瑞替加滨也比600毫克/天的瑞替加滨显著更有效。反应率定义为癫痫发作频率降低≥50%的患者比例,瑞替加滨900毫克/天和1200毫克/天组的患者反应率显著高于接受安慰剂的患者。在临床试验中,中枢神经系统(CNS)相关不良事件是与瑞替加滨相关的最常见的治疗中出现的不良事件。在大型II期试验的所有三个瑞替加滨组中,嗜睡(20.3%)、头晕(14.6%)、意识模糊(12.3%)和言语障碍(11.3%)是最常见的CNS相关不良事件。