Electrophysiological effects of a new antiarrhythmic substance Bonnecor (AWD 19-166, GS 015) on mammalian myocardium.
A new antiarrhythmic acting drug (Bonnecor, AWD 19-166, GS 015, 3- Carbethoxyamino-5-dimethyl-amino-acetyl-iminodibenzyl -hydrochloride) was tested electrophysiologically on isolated sinus node preparations and right ventricular papillary muscle of the rabbit. Transmembrane potentials were measured using a standard microelectrode technique. The substance was tested within a concentration range between 0.1 and 10 mg/l (2.5 X 10(-7) to 2.5 X 10(-5) mol/l). AWD 19-166 exerted negative chronotropic effects due to decreasing of the slope of the diastolic depolarization in sinus node cells. In ventricular myocardium AWD 19-166 increased the threshold strength of stimulation, prolonged the duration of action potentials at 90% but shortened it at 25% repolarization. The maximum upstroke velocity was found to be depressed. The maximum overshoot potential was diminished inspite of a drug-induced hyperpolarization of the resting transmembrane potential. Analysis of membrane responsiveness due to premature stimulation showed a concentration-dependent delay in the restitution of the maximum upstroke velocity of the premature action potentials and both a flattening and a shift towards more negative potentials of the potential-responsiveness relationship. AWD 19-166 decreased both the maximum upstroke velocity and the duration of Ca-mediated action potentials in concentrations between 2 and 8 mg/l. It is concluded that AWD 19-166 is able to exert potent antiarrhythmic effects in influencing both the fast and slow channel activity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D003984:Dibenzazepines; C048166:tiracizine; D002118:Calcium