Almotriptan, a new anti-migraine agent: a review.
Almotriptan is a new anti-migraine agent with nanomolar affinity for human 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and 5-HT(7) receptors and no significant affinity for more than 20 other pharmacological receptors. Almotriptan was effective in animal models predictive of anti-migraine activity in humans and had a good safety profile in animal studies. From the toxicological point of view, almotriptan has a profile similar to that of other marketed triptans. In animal studies, at levels substantially higher than required for therapeutic activity in humans, almotriptan was devoid of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major metabolic route and by flavin monooxygenase as the minor route. No dose adjustment is required for gender or age, and only in the case of severe renal impairment the dose should not exceed 12.5 mg over a 24-h period. There was no significant interaction between a single dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. The efficacy of almotriptan in the treatment of acute migraine was demonstrated in clinical trials on more than 3000 patients with migraine. At two h after oral administration of almotriptan, 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64 and 36%, respectively. The effects of almotriptan were significantly better than those of placebo. When almotriptan was administered in the early phase of migraine, the percentage of pain-free patients at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study, the incidence of adverse events with almotriptan was not statistically different from that of placebo. Based on the available data, it appears that almotriptan is the triptan of choice when good efficacy and high tolerability are desired.
D000818:Animals; D019540:Area Under Curve; D002319:Cardiovascular System / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D008881:Migraine Disorders / Q000188:drug therapy*; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology; D012137:Respiratory System / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014363:Tryptamines
D007211:Indoles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan