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 ...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.展开更多
文摘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.
