The effect on atrial and ventricular intracellular potentials, and other pharmacological actions of L9146, a non-halogenated benzo(b)thiophene related to amiodarone.

Abstract

L9146 was synthesised in the hope of eliminating the unwanted side-effects of amiodarone which has been shown to be effective in the control of atrial fibrillation, flutter, and in pre-excitation syndromes such as Wolff-Parkinson-White syndrome. L9146 has pharmacological and electrophysiological effects similar to those of amiodarone. It is an antagonist of both alpha and beta adrenoceptor-mediated cardiovascular effects of a noncompetitive type. It lowers vascular resistance briefly, and causes a longer lasting bradycardia. It moderately reduces the maximum rate of depolarisation (MRD), conduction velocity, and totally suppresses ventricular pacemakers activated by high doses of isoprenaline. In addition, L9146 greatly prolongs action potential duration (APD) in atrial and ventricular muscle. In normal ventricular conducting tissue the action potential duration (APD) is shorter in the bundle of His than in the false tendons, and shorter still in the ventricular muscle. L9146 lengthened APD throughout, but particularly in the proximal portion, and even more in the muscle, so that APD became uniform. The decrement of conduction of premature action potentials was increased to the point at which slowly conducting premature AP's were eliminated altogether.