5HT1F- and 5HT7-receptor agonists for the treatment of migraines.
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| 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.
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| Authors | Reto M Agosti |
| Journal | CNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 6 Issue 4 Pg. 235-7 (Aug 2007) ISSN: 1871-5273 [Print] United Arab Emirates |
| PMID | 17691977 (Publication Type: Journal Article, Review) |
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