New AMPA/KA antagonist shows early promise in migraine

Early results with a candidate drug that is designed to act on glutamergic hyperactivity have been positive enough to warrant further studies, a research group in the USA has reported.LY293558, the new drug, is an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist which has proven effective in preclinical models. Dr. Nabih M. Ramadan, now at Finch University of Health Sciences and formerly from Eli Lilly, and colleagues tested LY293558 in what they describe as a randomized, triple-blind, parallel-group, double-dummy trial.Patients with acute migraine were given 1.2 mg/kg intravenous LY293558, 6 mg subcutaneous sumatriptan, or placebo. The main measure of efficacy considered by the triallists was the headache score improvement from moderate/severe at baseline to mild/none at 2 hours. Of 45 enrolled patients, 44 completed the study, the authors report in Cephalalgia. They recorded response rates of 69% for LY293558 (P = 0.017 vs. placebo), 86% for sumatriptan (P "LY293558 and sumatriptan were superior to placebo on all other measures of improvement in pain and migraine associated symptoms," the authors report. They add that 15% of patients who took the new compound reported adverse events, one of which was severe. In contrast, 53% of patients who took sumatriptan (seven mild, one moderate) and 31% of those who received placebo reported adverse events. "The efficacy and safety results of LY293558 in this small migraine proof of concept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine," the authors conclude. "Larger trials are needed to further test the hypothesis."Reference...