TITLE

5HT1F- and 5HT7-Receptor Agonists for the Treatment of Migraines

AUTHOR(S)
Agosti, Reto M.
PUB. DATE
August 2007
SOURCE
CNS & Neurological Disorders - Drug Targets;2007, Vol. 6 Issue 4, p235
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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-HT1B/1D high affinity agonist, was introduced in the acute treatment of migraine. Although very efficient for migraine relief, activation of 5-HT1B receptor may also cause vasoconstriction outside brain, within the heart arteries for example. Unlike 5-HT1B, the 5-HT1D receptor is not located in vascular tissues but exclusively within neuronal, but high affinity agonists for 5-HT1D failed to prove clinical significance in randomized trials. The recent clone of 5-HT1F receptor together with data showing that sumatriptan exerts high affinity for this receptor subtype generated high expectations. Potent agonists for 5-HT1F 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-HT1F, another new cloned 5-HT subtype receptor, the 5-HT7 also attracts attention. Recently developed and clinically tested selective 5HT7 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.
ACCESSION #
25944825

 

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