title: Pilot study of MK-462 in migraine.
abstract: MK-462 is a potent, selective 5HT1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg (n = 8) and 40 mg (n = 36) vs placebo (n = 21), administered to 65 male and post-menopausal female migraine patients aged 22-51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly (p < 0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (40 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine.
authors.affiliation: California Clinical Trials, Beverly Hills, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Cutler
authors.forename: J
authors.initials: J
authors.lastname: Claghorn
authors.forename: J J
authors.initials: JJ
authors.lastname: Sramek
authors.forename: G
authors.initials: G
authors.lastname: Block
authors.forename: D
authors.initials: D
authors.lastname: Panebianco
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
authors.forename: S A
authors.initials: SA
authors.lastname: Reines
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000097:blood / Q000188:drug therapy*; D010147:Pain Measurement; D010865:Pilot Projects; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014363:Tryptamines
chemical_list: D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan