Pharmacological Profile of Antihypertensive Drugs with Serotonin Receptor and α-Adrenoceptor Activity

Research paper by P. A. van Zwieten, G. J. Blauw, P. van Brummelen

Indexed on: 23 Oct '12Published on: 23 Oct '12Published in: Drugs


During the last few years, several antihypertensive drugs with multiple actions have been introduced. Most of these hybrid drugs are β-adrenoceptor blockers with an additional vasodilator component, such as labetalol, dilevalol, carvedilol and celiprolol.A second category of antihypertensive drugs with multiple actions consists of agents which interact simultaneously with serotoninergic receptors and gα-adrenoceptors. Urapidil, ketanserin, and a few experimental compounds related to these drugs are examples of this type of antihypertensive. They may be characterised pharmacologically as follows: (1) Ketanserin is a selective antagonist of serotonin2 receptors with an additional much weaker α1-adrenoceptor antagonistic activity. Its well documented antihypertensive activity cannot be explained by either serotonin2-receptor blockade or α-adrenoceptor antagonism alone. An unknown type of interaction between serotonin-receptor and α1-adrenoceptor blockade appears to be necessary, either in the periphery or in the CNS. (2) Urapidil is a selective α1-adrenoceptor antagonist and, as such, a peripheral vasodilator. In addition, it displays central hypotensive activity, probably caused by the stimulation of serotonin1A receptors in the CNS. This component is probably additive to the peripheral effect, and is also the background to the lack of reflex tachycardia seen with urapidil.The modes of action of both types of drugs are discussed in connection with the role of serotonin and its receptors in the cardiovascular system, both at the peripheral and the CNS levels.