The Pharmacology of Specific, Pure and Potent Serotonin 5-HT2 or S2-Antagonists

Ketanserin was found to be a very active and well tolerated drug in the treatment of a surprising variety of acute and chronic disorders in man and in animals.

Abstract

Several members of the newly discovered ketanserin series of specific, pure and potent 5-HT2-antagonists are essential tools for studying the role of serotonin (5-HT) in a wide variety of physiological and pathological conditions in various animal species, including man. These compounds, of which ketanserin (R 41 468) is the prototype, bind primarily and with high affinity to 5-HT2 receptors and not to 5-HT1 receptors. They are specific competitive antagonists of 5-HT-induced arterial and venous vasoconstriction, bronchoconstriction and platelet aggregation. They are completely devoid of serotoninomimetic activity. Ketanserin itself fails to cross the blood-brain barrier to any significant extent, whereas other members of the series, e. g. pirenperone, act on the brain and are potent antagonists of LSD and other centrally acting serotoninomimetic drugs. Several members of the series are fast and long acting drugs with a very high safety margin and are almost as active orally as by parenteral administration. Ketanserin was found to be a very active and well tolerated drug in the treatment of a surprising variety of acute and chronic disorders in man and in animals. The role of 5-HT in the etiology of these pathological states is discussed.