| Abstract
| - Several 5-HT1D/1B receptor agonists are now entering the marketplace as treatments formigraine. This paper describes the development of selective h5-HT1D receptor agonists aspotential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80 (L-772,405),a high-affinity h5-HT1D receptor full agonist having 170-fold selectivity for h5-HT1D receptorsover h5-HT1B receptors. L-772,405 also shows very good selectivity over a range of otherserotonin and nonserotonin receptors and has excellent bioavailability following subcutaneousadministration in rats. It therefore constitutes a valuable tool to delineate the role of h5-HT1Dreceptors in migraine. Molecular modeling and physical properties have been utilized topostulate the binding conformation of these compounds in the receptor cavity.
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