title: 5HT1F- and 5HT7-receptor agonists for the treatment of migraines.
abstract: Serotonin was the first neurotransmitter believed to be involved in cephalic pain transfer forward to the cortex, but the precise mechanism was confirmed only after sumatriptan, a 5-HT(1B/1D0) high affinity agonist, was introduced in the acute treatment of migraine. Although very efficient for migraine relief, activation of 5-HT(1B) receptor may also cause vasoconstriction outside brain, within the heart arteries for example. Unlike 5-HT(1B), the 5-HT(1D) receptor is not located in vascular tissues but exclusively within neuronal, but high affinity agonists for 5-HT(1D) failed to prove clinical significance in randomized trials. The recent clone of 5-HT(1F) receptor together with data showing that sumatriptan exerts high affinity for this receptor subtype generated high expectations. Potent agonists for 5-HT(1F) receptors were effective in animal models for migraine and later clinical trials showed efficacy even in humans, introducing the first line future anti-migraine drugs. Apart from 5-HT(1F), another new cloned 5-HT subtype receptor, the 5-HT(7) also attracts attention. Recently developed and clinically tested selective 5HT(7) antagonists SB-269970-A and SB-656104-A suggest that the receptor may play a role in other CNS disorders including anxiety and cognitive disturbances, suggesting a potential role for the migraine prophylaxis. These data and speculations are discussed in details in this paper with special references.
authors: Board Certified Neurologist, Headache Center Zurich Hirslanden, Zurich, Switzerland. Reto.agosti@kopfwww.ch
authors: Reto M
authors: RM
authors: Agosti
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000235:genetics; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D000096642:Receptor, Serotonin, 5-HT1F
chemical_list: D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F; C104425:serotonin 7 receptor