Effects on transmembrane action potential, slow inward current and force of contraction in ventricular cardiac muscle of BRL 31660, a new antiarrhythmic drug with class I and class IV activity.

The effects of 1-30 mumol l-1 BRL 31660 on transmembrane action potential and force of contraction were investigated in guinea-pig electrically driven papillary muscles. Lidocaine was studied for comparison. BRL 31660 depressed Vmax of the action potential without changing the resting potential, decreased the force of contraction and decreased the action potential duration. Similar effects were obtained with lidocaine. BRL 31660 inhibited the recovery of Vmax from inactivation, the time constant of which was estimated to be about 1,100 ms in the presence of 10 mumol l-1 BRL 31660. The depressive effect on Vmax was particularly pronounced at low (less negative) membrane potentials. BRL 31660 can thus be classified as a class I antiarrhythmic agent of the lidocaine type. Additional voltage-clamp experiments in cow ventricular trabeculae provided evidence that BRL 31660 also depressed the slow inward current at concentrations similar to those producing the effects on the transmembrane action potential. BRL 31660 thus exerted an additional class IV action. This effect was not shared by lidocaine. It is concluded that BRL 31660 is a new antiarrhythmic agent which depresses both the fast and slow inward current at similar concentrations. The dual effects of BRL 31660 conceivably contribute to its antiarrhythmic activity, but the clinical relevance of these results remains to be elucidated.