INFLUENCE OF α1‐ADRENOCEPTOR ANTAGONISM OF KETANSERIN ON THE NATURE OF ITS 5‐HT2 RECEPTOR ANTAGONISM

Abstract

1. In order to investigate alpha 1-adrenoceptor interactions with 5-HT2 receptors, the effect of ketanserin (which antagonizes both types of the above receptors) on responses to 5-hydroxytryptamine (5-HT) and phenylephrine (PE) was measured in isolated perfused rat tail arteries. 2. Ketanserin was found to be a competitive antagonist at 5-HT2 receptors (pA2 = 9.19) and alpha 1-adrenoceptors (pA2 = 7.52). 3. Ritanserin, an analogue of ketanserin with very weak alpha 1-adrenoceptor antagonist activity, was found to be a potent non-competitive 5-HT2 receptor antagonist. 4. In the presence of the potent alpha 1-adrenoceptor antagonist prazosin, ketanserin was a non-competitive 5-HT2 receptor antagonist. 5. Thus, for ketanserin to exhibit competitive 5-HT2 receptor antagonism, its coexisting alpha 1-adrenoceptor antagonist property appears mandatory.