YM-12617, 5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2-methoxybenzenesulfonamide HCl is structurally novel, an extremely potent and highly selective alpha 1-adrenoceptor antagonist. An asymmetric center exists at the alpha-carbon atom in the phenethylamine portion of YM-12617, therefore two optical enantiomers exist. alpha-Adrenoceptor blocking properties and hypotensive activities of YM-12617 and its enantiomers have been compared in vitro and in vivo. 1. In the isolated rabbit aorta, R(-)- and S(+)-YM-12617 competitively antagonized phenylephrine-induced contraction with pA2 values of 9.95 and 7.69, respectively. Although R(-)- and S(+)-YM-12617 were also competitive antagonists toward UK-14,304 at prejunctional alpha 2-adrenoceptors in the isolated guinea-pig ileum, the affinities of R(-)-YM-12617 (pA2 = 6.18) and S(+)-YM-12617 (pA2 = 5.64) for these receptors were 5,900 and 110 times lower than those displayed for postjunctional alpha 1-adrenoceptors in the isolated rabbit aorta. 2. R(-)- and S(+)-YM-12617 displaced both 3H-prazosin and 3H-idazoxan binding to rat brain membranes; however, the affinities of the R(-)- and S(+)-enantiomers for alpha 1-adrenoceptors (pKi = 9.95 and 7.83, respectively) were 21,000 and 72 times higher than those for alpha 2-adrenoceptors (pKi = 5.62 and 5.97), respectively. 3. Based on pA2 values obtained in the isolated tissues and pKi values in the binding assays, R(-)-YM-12617 was 132-182 times more potent than S(+)-YM-12617 as an antagonist at alpha 1-adrenoceptors. In contrast, the R(-)- and S(+)-enantiomers were similar in potency at blocking alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)