158930-09-7

Cerebral vasodilatation and neurogenic inflammation are considered to be prime movers in the pathogenesis of migraine. Activation of 5-HT _1B reverses cerebral vasodilatation and activation of 5-HT _1D prevents neurogenic inflammation. Frovatriptan has a high affinity for 5-HT _1B and 5-HT _1D receptors and a moderate affinity for the 5-HT _1A and 5-HT _1F receptors subtypes. Frovatriptan has a moderate affinity for the 5-HT ₇ receptors, an action associated with coronary artery relaxation in the dog.

Oral bioavailability of Frovatriptan is 22%-30% and is not affected by food. Although the maximum concentration in the plasma is achieved in 2-3 hours, 60%-70% of this is achieved in 1 hour. A steady state is achieved in 4-5 days. Plasma protein binding is low at 15%. The most unique feature is the relative terminal long half-life of about 26 hours. Frovatriptan is chiefly metabolized by CYP1A2 and is cleared by the kidney and liver making moderate failure of either organ not a limiting factor in treatment.
Frovatriptan (0.1, 0.2, and 0.3 mg/kg; a single bolus intraduodenal administration) treatment produces an increase in carotid vascular resistance, which is sustained for at least 5 hours in dogs.