Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan.
OBJECTIVE
To determine the pharmacological profile of frovatriptan.


BACKGROUND
Frovatriptan is a new 5-HT(1B/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-HT(1B) and 5-HT(1D) receptors, and moderate affinity for 5-HT(1A), 5-HT(1F), and 5-HT(7) receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT(1B) and 5-HT(1D) receptors, and as a moderately potent full agonist at 5-HT(7) 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.


CONCLUSIONS
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.
Comer
M B
MB
Vernalis Ltd, Wokingham, Berkshire, UK.
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D011817:Rabbits; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D014363:Tryptamines; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002227:Carbazoles; C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; C108128:frovatriptan