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.
Electrophysiological effects of cyclopropylmethyl 4-(3-nitrophenyl) 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (MPC-2101), a newly synthetized 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 maximum 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 the plateau 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+]o and histamine at 10(-6) M, but at 3 x 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 x 10(-6) M, showed frequency-dependent depression in dV/dt of the slow action potentials. MPC-2101 showed less potent actions than nicardipine on electrophysiological activities of the SA node and papillary muscle.
Kano
T
T
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
Nakamura
S
S
Nishi
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects
D002121:Calcium Channel Blockers; D000431:Ethanol; C059064:MPC 2101; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium