In vitro isolated tissue studies with atiprosin (AY-28,228): a new antihypertensive compound.
Using in vitro isolated tissue and binding studies we have defined a receptor activity profile for atiprosin. The most prominent action of the compound was significant alpha-adrenoceptor antagonist activity (pA2 = 8.11) that was less potent than prazosin (pA2 = 8.78) but more potent than either ketanserin (pA2 = 7.34) or indoramin (pA2 = 7.85). In addition, atiprosin was selective for alpha 1-adrenoceptors, since the compound was over 100-fold less potent as an antagonist at alpha 2-adrenoceptors (pA2 = 6.04). Atiprosin also displayed selective serotonin 5-HT2-receptor antagonist activity similar to that seen with ketanserin, but with a lesser potency (pA2 atiprosin, 6.87; ketanserin, 8.61). Although atiprosin also displayed significant histamine H1-antagonist activity (pA2 = 7.32), it was less potent as an H1-antagonist than as an alpha 1-adrenoceptor antagonist. In contrast, both indoramin and ketanserin displayed H1-antagonist activity (pA2 8.77 and 8.83, respectively) greater than their respective alpha 1-adrenoceptor antagonist activities. Atiprosin had little or no activity at either beta 1- or beta 2-adrenoceptors, muscarinic or histamine H2-receptors, nor any marked ability to produce smooth muscle relaxation either by a direct effect or via calcium entry blockade.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004285:Dogs; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D006634:Histamine H1 Antagonists; D007211:Indoles; D012702:Serotonin Antagonists; C054073:atiprosin