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 a cute migraine, but the side-effect of coronary vasoconstriction restricts t heir use in patients who are at risk of coronary artery disease. We have st udied the efficacy of LY334370, a selective serotonin 1F (5-HT1F) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine rel ief. Methods We gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients w ith moderate or severe migraine headaches in a double blind, parallel group study. We measured efficacy by sustained response, response at 2 h, pain f ree 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 o f 26 (8%), three of 22 (1.4%), 11 of 30 (37%), and 11 of 21 (52%) (dose res ponse 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, eig ht of 30 (27%), and eight of 21 (38%) (p=0.001): sustained pain free, one o f 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 th ree of 15 (20%). More patients given LY334370 than placebo reported astheni a, somnolence, and dizziness. Interpretation Our findings show that LY334370 is effective in treatment of acute migraine through selective trigeminovascular neuronal inhibition.