KMD-3213, a novel alpha(1A)-adrenoceptor antagonist, potently inhibits the functional alpha(1)-adrenoceptor in human prostate

KMD-3213, (-)-(R)- 1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxylethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha(1A)-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha(1) -adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha(1)-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 alpha(1)-adrenoceptors is given as potency for the alpha(1L)-adrenoceptor with an estimated pA(2) value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha(1A)-adrenoceptor-selective antagonist, has strong affinity for the alpha(1L)-adrenoceptor in the human prostate. (C) 1997 Elsevier Science B.V.