Effects of a newly synthetized calcium antagonist, cyclopropylmethyl 4- (3-nitrophenyl) 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (MPC-2101) , on action potentials of rabbit's myocardial tissues in vitro
Kano, T.; Nakamura, S.; Nishi, K.
Archives Internationales de Pharmacodynamie et de Therapie 296: 101-117
1988
ISSN/ISBN: 0003-9780 PMID: 3240014 Document Number: 307931
Electrophysiological effects of cyclopropylmethyl 4-(3-nitrophenyl) 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (MPC-2101), a newly synthesized compound, were examined in the rabbit SA node and papillary muscle, using a conventional microelectrode technique in vitro. In the SA node, MPC-2101 (10-8-10-6 M) showed dose-dependent negative chronotropic effects by depressing the slope of slow diastolic repolarization without significant effects on maximuim diastolic potential and action potential duration. MPC-2101 (10-7-10-5 M) had no significant effects on the resting membrane potential, the amplitude and dV/dt of action potentials in papillary muscles, but induced a statistically significant reduction of theplateau phase of the action potential duration measured at 20% repolarization at a concentration of 10-5 M. MPC-2101, at concentrations lower than 10-6 M, had no significant effects on the amplitude, dV/dt, or duration of slow action potentials induced in 18 mM [K+]0 and histamine at 10-6 M, but at 3 .times. 10-6 M significantly depressed all parameters of the slow action potentials. In higher Ca2+ solution, dose-response curves for MPC-2101 on dV/dt of slow action potentials were shifted to the right. MPC-2101, at a concentration of 3 .times. 10-6 M, showed frequency-dependent depression in dV/dt of the slow action potentials. MCP-2101 showed less potent actions than nicardipine on electrophysiological activities of the SA node and papillary muscle.