Pharmacology of Potent and Selective S2-Serotonergic Antagonists

Ketanserin is the prototype of a new series of serotonergic antagonists that competitively and selectively block 5-hydroxytryptamine (S2) serotonergic receptors. Ketanserin and its analogues antagonize the events mediated by this receptor, i.e., serotonin-induced vasoconstriction, bronchoconstriction, and platelet aggregation, irrespective of whether serotonin acts directly or amplifies the effect of vasoconstrictors or platelet aggregating agents. The antagonism is pure because compounds such as ketanserin are devoid of agonistic activity. The actions of ketanserin are mainly peripheral, whereas other members of the series, e.g., ritanserin, act on the brain and are potent antagonists of lysergic acid diethylamide and other centrally acting serotonomimetic drugs. The different pharmacological profiles of the new S2-serotonergic antagonists and the evidence already available on their clinical effects prompt a further exploration of these agents in a large range of cardiovascular and other diseases.