Functions of 5-HT2A receptor and its antagonists in the cardiovascular system

The serotonin (5-hydroxytryptamine, 5-HT) receptors have conventionally been divided into seven subfamilies, most of which have several subtypes. Among them, 5-HT2A receptor is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Accordingly, selective 5-HT2A antagonists may have potential in the treatment of cardiovascular diseases. Sarpogrelate, a selective 5-HT2A antagonist, has been introduced clinically as a therapeutic agent for the treatment of ischemic diseases associated with thrombosis. Molecular modeling studies also suggest that sarpogrelate is a 5-HT2A selective antagonist and is likely to have pharmacological effects beneficial in the treatment of cardiovascular diseases. This review describes the above findings as well as the signaling linkages of the 5-HT2A receptors and the mode of agonist binding to 5-HT2A receptor using data derived from molecular modeling and site-directed mutagenesis. (C) 2004 Elsevier Inc. All rights reserved.