The 5-HT2 receptor antagonist, pelanserin, inhibits alpha 1-adrenoceptor-mediated vasoconstriction in vitro.
The antagonism by pelanserin (2,4(1H,3H)-quinazolinedione,3-[3-(4-phenyl-1- piperazinyl)-propyl]-HCl), a potent 5-HT2 receptor antagonist, of alpha 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 alpha 1-adrenoceptor agonist methoxamine elicited concentration-dependent contractions in all four arterial rings, an effect which was competitively antagonized by pelanserin. pA2 values for pelanserin were in the 7.67-8.11 range when evaluated against the alpha 1-adrenoceptor agonist in arteries from normotensive or hypertensive rats. These data support the conclusion that pelanserin displays alpha 1-adrenoceptor blocking properties. The ability of the 5-HT2 receptor antagonist pelanserin to additionally block alpha 1-adrenoceptor-mediated constriction in different vessels of WKY and SHR may potentially contribute to its blood pressure lowering effects.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013623:Tail / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; C043157:pelanserin; D008729:Methoxamine