KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the functional alpha1-adrenoceptor in human prostate

Abstract

KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1-adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213 inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45 +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L-adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist, has strong affinity for the alpha1L-adrenoceptor in the human prostate.