Pharmacology of the Selective 5-HT1B/1D Agonist Frovatriptan


Address all correspondence to M.B. Comer, Vernalis Ltd, Oakdene Court, 613 Reading Road, Winnersh, Wokingham, Berkshire RG41 5UA, UK.


Objective.—To determine the pharmacological profile of frovatriptan.

Background.—Frovatriptan is a new 5-HT1B/1D agonist developed for the treatment of migraine.

Methods.—Pharmacological studies were performed using in vitro and in vivo techniques.

Results.—Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT1B and 5-HT1D receptors, and moderate affinity for 5-HT1A, 5-HT1F, and 5-HT7 receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT1B and 5-HT1D receptors, and as a moderately potent full agonist at 5-HT7 receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow.

Conclusion.—The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects.