In Vitro Isolated Tissue Studies with Atiprosin (AY-28,228)

Abstract

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.