The 5-HT2 receptor antagonist, pelanserin, inhibits α1-adrenoceptor-mediated vasoconstriction in vitro

The antagonism by pelanserin (2,4(1 H ,3 H )-quinazolinedione,3-[3-(4-phenyl-1-piperazinyl)-propyl]-HCl), a potent 5-HT 2 receptor antagonist, of α 1 -adrenoceptor-mediated contractions of endothelium-denuded carotid, aorta, mesenteric and caudal arteries of both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was investigated. The selective α 1 -adrenoceptor agonist methoxamine elicited concentration-dependent contractions in all four arterial rings, an effect which was competitively antagonized by pelanserin. pA 2 values for pelanserin were in the 7.67–8.11 range when evaluated against the α 1 -adrenoceptor agonist in arteries from normotensive or hypertensive rats. These data support the conclusion that pelanserin displays α 1 -adrenoceptor blocking properties. The ability of the 5-HT 2 receptor antagonist pelanserin to additionally block α 1 -adrenoceptor-mediated constriction in different vessels of WKY and SHR may potentially contribute to its blood pressure lowering effects.