Electrophysiological characterization of class III activity of a verapamil derivative in guinea-pig cardiac tissues.
In isolated guinea-pig papillary muscle ([K+]o: 4.7 mmol/l, stimulation rate: 1 Hz) the verapamil derivative NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine)-HCl (YS035; 0.3-100 mumol/l) increased the action potential duration measured at 90% repolarization level (APD90) up to 132% of control and enhanced the force of contraction (Fc) up to 125% of control while resting potential (RP) and the maximum upstroke velocity (Vmax) remained nearly unchanged. At 300 mumol/l YS 035, the membrane became depolarised and action potentials could no longer be elicited. These effects were reversed during wash-out. The increase of ADP90 was largest at 0.05 Hz, and the drug-induced effect continuously declined with an increase in stimulation frequency to 2 Hz. Control ADP90 was correlated to the absolute increase of ADP90 (r = 0.84). In atrial muscle the effect of YS 035 on APD90 was more pronounced than in papillary muscle. The Vmax of slow responses ([K+]o: 27 mmol/l, [Ba2+]o: 0.5 mmol/l) was not affected by concentrations as high as 30 mumol/l YS 035, whereas APD90 was enhanced. An increase in the stimulation rate (0.05 to 0.33 Hz) induced only a small decrease of Vmax at 100 mumol/l YS 035. According to this electrophysiological characterisation YS 035 shows Class III antiarrhythmic properties.
Kammer
T
T
Institute of Pharmacology, University of Düsseldorf Fed. Rep. of Germany.
Berger
F
F
Borchard
U
U
Hafner
D
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010627:Phenethylamines; C041094:N,N-bis(3,4-dimethoxyphenethyl)-N-methylamine; D014700:Verapamil