A propanolamine derivative with vanillylamide base, KMUP 880602, was first investigated under in vivo and in vitro conditions. IV KMUP 880602 (0.1, 0.5, 1.0, and 2.0 mg/kg) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880602 also markedly inhibited both the tachycardia effects induced by (-)isoproterenol and arterial pressor responses induced by phenylephrine. In isolated guinea pig tissues, KMUP 880602 competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses. The apparent pA2 values KMUP 880602 were 7.24 +/- 0.08 (right atria), 7.42 +/- 0.07 (left atria), and 6.24 +/- 0.06 (trachea). KMUP 880602 also produced a competitive antagonism of norepinephrine-induced contraction in the isolated rat aorta with pA2 values of 7.64 +/- 0.18. In the radioligand-binding assay, [3H]CGP-12177 binding to rat ventricle and lung tissues and [3H]prazosin binding to brain membranes were inhibited by KMUP 880602 with pKi values of 7.27, 6.08, and 8.25, respectively. In isolated rat thoracic aorta, the vasorelaxant effects of KMUP 880602 on phenylephrine-induced contractions were attenuated by pretreatment with tetraethylammonium (10-3 M) and charybdotoxin (10-7 M) but not by glibenclamide, 4-aminopyridine, and apamin. In conclusion, KMUP 880602 is an alpha/beta-adrenoceptor blocker, with selective beta1-adrenoceptor blocking and vascular smooth muscle relaxation activities. Particularly, the vasorelaxant effect of KMUP 880602 is partially mediated by the opening of charybdotoxin-sensitive K+ channel.