Frovatriptan, sold under the brand name Frova among others, is a triptan medication developed by Vernalis for the treatment of migraine headaches and for short term prevention of menstrual migraine. The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.
Medical uses Frovatriptan is used in the treatment of migraine.
Available forms It is available as 2.5 mg tablets.
Contraindications Frovatriptan should not be given to patients with:
Ischemic heart disease Cerebrovascular syndrome Peripheral vascular disease Uncontrolled hypertension Hemiplegic or basilar migraine
Side effects Rare, but serious cardiac events have been reported in patients with risk factors predictive of CAD. These include: coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation.
Pharmacology Pharmacodynamics
+ Target Affinity (Ki, nM) 5-HT1A 50–62 (Ki)759–>10,000 ()38% () 5-HT1B 2.5–46 (Ki)6.3–20 ()92% () 5-HT1D 1.7–10 (Ki)2–5 ()98% () 5-HT1E >1,000 (Ki)6,610–>10,000 ()44% () 5-HT1F 63–120 (Ki)79–447 ()46% () 5-HT2A >10,000 (Ki)>10,000 () 5-HT2B >10,000 (Ki)>10,000 () 5-HT2C >5,000 (Ki) () 5-HT3 >1,000 (mouse/rat) 5-HT4 5-HT5A 5-HT6 5-HT7 107–200 (Ki)38 () α1 >10,000 (rat) α1A–α1D α2A–α2C β1–β3 D1 >10,000 D2 >10,000 D3 >10,000 D4–D5 H1 >10,000 (guinea pig) H2–H4 M1–M5 I1, I2 σ1, σ2 Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:
Frovatriptan is a serotonin receptor agonist, with high affinity for the serotonin 5-HT1B and 5-HT1D receptors and with weaker activity at the serotonin 5-HT1F receptor. It has no significant effects on the GABAA mediated channel activity and benzodiazepine binding sites. Frovatriptan inhibits excessive dilation of arteries that supply blood to the head. Uniquely among most triptans, frovatriptan is also a relatively potent serotonin 5-HT7 receptor agonist. It is inactive at the serotonin 5-HT2A and 5-HT2B receptors.
Pharmacokinetics Frovatriptan has a terminal elimination half-life of approximately 26 hours, making it the longest within its class.
Chemistry Frovatriptan's chemical structure is unusual among triptans, with other triptans being simple tryptamines or closely related compounds but frovatriptan instead being a tricyclic cyclized tryptamine and tetrahydrocarbazolamine derivative. It can be thought of as a 5-substituted and side chain-cyclized derivative of N-methyltryptamine (NMT).
The experimental log P of frovatriptan is 0.9 and its predicted log P is 1.2.
History Frovatriptan was first described in the scientific literature by 1997.Brown, A. M., Parsons, A. A., Raval, P., Porter, R., Tilford, N. S., Gager, T. L., ... & King, F. D. (1996, October). SB 209509 (VML 251), a potent constrictor of rabbit basilar artery with high affinity and selectivity for human 5-HT1D receptors. In BRITISH JOURNAL OF PHARMACOLOGY (Vol. 119, pp. P110-P110). It was approved for medical use in the United States in 2001.
Society and culture Legal status Frovatriptan is available only by prescription in the United States and Canada.
See also Triptan Tetrahydrocarbazolamine LY-344864
References