Ca antagonistic properties of mepirodipine hydrochloride [+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl methyl 2,6-dimethyl-4- (m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride, YM-09730-5) were assessed by studying the pharmacological actions and binding characteristics of the drug in the stem coronary artery. IC50 values of YM-09730-5 (3.5 x 10(-10) mol/l) and nifedipine (6.6 x 10(-9) mol/l) for 40 mmol/l K-induced tonic contraction of pig coronary artery indicated that YM-09730-5 was about 20 times more potent than nifedipine in Ca antagonistic action. However, YM-09730-5 showed an onset of inhibitory action 3 to 5 times slower than nifedipine. A 40-min preincubation of the target tissue with YM-09730-5 also inhibited the contractions produced by acetylcholine, histamine, 5-hydroxytryptamine, and high Ca, and pD2' values were between 8.0 and 7.0; while nifedipine was less potent. The specific binding of [3H]nitrendipine to the membrane of pig coronary artery was inhibited by YM-09730-5, thereby indicating that [3H]nitrendipine and YM-09730-5 compete for the similar receptor sites of dihydropyridine-sensitive Ca channels. Suppression of high K-, Ca- and agonist-induced contractions by YM-09730-5 (3 x 10(-9) mol/l-10(-7) mol/l) remained even after washings at 20-min intervals for more than 3 h; and, in particular at a high concentration of YM-09730-5, the suppression was slightly antagonized by excess Ca or a Ca-agonist. The contraction inhibited by nifedipine, on the other hand, was readily restored by several washings.(ABSTRACT TRUNCATED AT 250 WORDS)