Effects of the novel antiarrhythmic compound TR 2985 (ropitoin) on action potentials of different mammalian cardiac tissues.

Abstract

Ropitoin (TR 2985) is a novel antiarrhythmic drug. In the present work we have found that the main effect of the compound on the normal action potential of different cardiac tissues, guinea-pig atrial and ventricular muscle (1-3 mumol/l), and dog Purkinje fibres (0.5-1.0 mumol/l) was a depression of the maximum upstroke velocity. This effect was dependent on the frequency of stimulation, being stronger at higher frequencies. In the presence of the drug (3 mumol/l), we observed a shift of 9 mV of the resting membrane potential-maximum upstroke velocity relationship to more negative potentials. Under control conditions recovery from inactivation of maximum upstroke velocity was complete in less than 200 ms. Ropitoin induced a very slow component of recovery of the maximum upstroke velocity, explaining the frequency-dependent effects of the drug. The slow recovery of the maximum upstroke velocity induced by ropitoin was dependent on the membrane potential being faster at a more hyperpolarized membrane potential. The time course of the recovery was also dependent on pH; acidosis slowed it considerably. Ropitoin increased action potential duration of atrial muscle at 20% and 90% of repolarization. In contrast, the compound shortened action potential duration of ventricular muscle at 20% and 90% of repolarization, and dog Purkinje fibres at 50% and 90% of repolarization. In addition, ropitoin (1-3 mumol/l) depressed guinea-pig ventricular slow action potentials. This effect was the stronger the higher the stimulation frequency.