一种新型AMPA/GluR5受体拮抗剂LY293558对急性偏头痛患者有效且耐受性良好

作     者：Ramadan N.M. Wallihan R.G. 黄卫东 

作者机构：Finch University of Health Sciences Chicago Medical School 33 33 Green Bay Road North Chicago IL 60064 United States 

出 版 物：《世界核心医学期刊文摘（神经病学分册）》 (Digest of the World Core Medical Journals:Clinical Neurology)

年 卷 期：2005年第1卷第2期

页      面：12-13页

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

主　　题：偏头痛患者 AMPA/GluR5 LY293558 受体拮抗剂 舒马曲坦 安慰剂 三盲 试验研究结果 反应率 大样本研究 

摘      要：Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY29355 8, an α amino 3 hydroxy 5 methyl 4 isox azolepropionic acid (AMPA)/kain ate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple blind, parallel group, double d ummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneou s (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary e fficacy variable was the headache response rate, i.e. headache score improvement from mod erate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients , 44 patients (20M:24F; mean age ±.SD = 40 ±.9 years) completed the study. Res ponse rates were 69%for LY293558 (P = 0.017 vs. placebo), 86%for sumatriptan ( P .0.01 vs. placebo) and 25%for placebo. LY293558 and sumatriptan were superi or to placebo (P .0.01 for all comparisons) on all other measures of improveme nt in pain and migraine associated symptoms. Fifteen percent of patients who too k LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty t hree percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31%of those who received placebo reported AEs (n = 5; four mild, one severe ). The efficacy and safety results of LY293558 in this small migraine proof of c oncept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.