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Keywords:

Action Potentials, Animals, Anti-Arrhythmia Agents, Calcium, Dibenzazepines, Female, Heart, Heart Rate, In Vitro, Male, Rabbits, Sinoatrial Node, Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Chemistry, Medicinal, Chemistry, Multidisciplinary, Pharmacology & Pharmacy, Chemistry, In Vitro Techniques, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

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.