Influence of alpha 1-adrenoceptor antagonism of ketanserin on the nature of its 5-HT2 receptor antagonism.
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.
Marwood
J F
JF
Clinical Pharmacology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013623:Tail / Q000098:blood supply
D058668:Adrenergic alpha-1 Receptor Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D012110:Reserpine; D007650:Ketanserin; D011224:Prazosin