Selective seratonin 1F (5-HT1F) receptor agonist LY334370 for acute migraine:: a randomised controlled trial

Background Triptans (5-HT1B/1D receptor agonists) are effective drugs for acute migraine, but the side-effect of coronary vasoconstriction restricts their use in patients who are at risk of coronary artery disease. We have studied the efficacy of LY334370, a selective serotonin 1F (5-HT1F) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine relief. Methods We gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients with moderate or severe migraine headaches in a double blind, parallel group study. We measured efficacy by sustained response, response at 2 h, pain free at 2 h, and sustained pain free. Findings The proportions of patients with defined endpoints for placebo and LY334370 20, 60, and 200 mg, respectively, were: sustained response, two of 26 (8%), three of 22 (1.4%), 11 of 30 (37%), and 11 of 21 (52%) (dose response p<0.001); response, five of 26 (19%), four of 22 (18%), 15 of 30 (50%), and 15 of 21 (71%) (p<0.001); pain free, one of 26 (4%), none of 22, eight of 30 (27%), and eight of 21 (38%) (p=0.001): sustained pain free, one of 26 (4%), none of 22, seven of 30 (23%), and seven of 21 (33%) (P=0.002); recurrence rates, one of five (20%), none of four, four of 15 (27%), and three of 15 (20%). More patients given LY334370 than placebo reported asthenia, somnolence, and dizziness. Interpretation Our findings show that LY334370 is effective in treatment of acute migraine through selective trigeminovascular neuronal inhibition.