mdl-100907 and Cardiovascular-Diseases

In view of the pivotal role of serotonin (5-HT) in a wide variety of cardiovascular disorders, extensive effort has been made to develop different types of 5-HT receptor antagonists for therapeutic use. On the basis of experimental studies, this article is focused on the potentials of sarpogrelate, a specific 5-HT2A receptor antagonist as an antiplatelet, antithrombotic, antiatherosclerotic and antianginal agent. The major effects of sarpogrelate are due to the inhibition of 5-HT-induced platelet aggregation and smooth muscle cell proliferation. This agent was found to attenuate the 5-HT-mediated increase in intracellular Ca2+ and ischemia-reperfusion injury in the heart. Sarpogrelate has been found to have beneficial effects in peripheral vascular disease, restenosis after coronary stenting, pulmonary hypertension, acute and chronic myocardial infarction.

Topics: Animals; Cardiovascular Diseases; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Serotonin 5-HT2 Receptor Antagonists; Succinates

The serotonin (5-hydroxytryptamine, 5-HT) receptors have conventionally been divided into seven subfamilies, most of which have several subtypes. Among them, 5-HT(2A) receptor is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Accordingly, selective 5-HT(2A) antagonists may have potential in the treatment of cardiovascular diseases. Sarpogrelate, a selective 5-HT(2A) 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-HT(2A) 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-HT(2A) receptors and the mode of agonist binding to 5-HT(2A) receptor using data derived from molecular modeling and site-directed mutagenesis.

Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Humans; Protein Binding; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists

Small drug-like molecules that can block the function of serotonin 5-HT

Topics: Animals; Cardiovascular Diseases; Humans; Isoxazoles; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Serotonin 5-HT2 Receptor Antagonists; Structure-Activity Relationship; Succinates; Vasoconstriction