title: Electrophysiological effects of OPC-88117, a new antiarrhythmic agent on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.
abstract: 1. The effects of OPC-88117, a new antiarrhythmic agent, on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, OPC-88117 above 3 x 10(-6) M caused a dose-dependent prolongation of action potential duration (APD). 3. OPC-88117 above 3 x 10(-5) M caused a significant decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 4. In the presence of OPC-88117, trains of stimuli at rates greater than or equal to 1.0 Hz led to a use-dependent inhibition of Vmax with rapid onset. The time constant for the recovery of Vmax from the use-dependent block was 456 ms. 5. The curves relating membrane potential and Vmax were shifted by OPC-88117 to the direction of more negative potentials (9 mV at 10(-4) M). 6. In single ventricular myocytes treated with OPC-88117 (1-3 x 10(-4) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that the primary electrophysiological effect of OPC-88117 on the cardiac muscle cell is prolongation of APD (Class III action) and that at high concentrations, it may also possess a lignocaine-like sodium channel inhibitory effect (Class I action).
authors.affiliation: Department of Circulation and Respiration, Nagoya University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Toyama
authors.forename: I
authors.initials: I
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Honjo
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010210:Papillary Muscles / Q000166:cytology / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D015363:Quinolones; C061263:8-methyl-3-(4-methyl-1-piperazinyl)-2(1H)-quinolinone