Comparative effects of bepridil, its quaternary derivative CERM 11888 and verapamil on caffeine‐induced contracture in ferret hearts

Abstract 1. The effects of bepridil, its quaternary derivative: CERM 11888 (methyl-pyrrolidinium bromide) (10(-7)-10(-5) M), and verapamil (10(-7)-10(-6) M) were compared on caffeine-induced contracture of isolated ventricular trabeculae of the ferret. 2. Bepridil diminished the amplitude of contracture in a concentration-dependent fashion, and this effect was significantly different from that of CERM 11888 which, like verapamil, only reduced the amplitude at the highest concentration used. 3. Bepridil (10(-6) M) significantly shortened the time to peak tension and accelerated the relaxation phase of contracture. This latter effect was different from that of CERM 11888. Verapamil (10(-6) M) also tended to accelerate the relaxation phase. At 10(-5) M these actions of bepridil on the time to peak and relaxation tended to reverse. 4. At all concentrations bepridil and verapamil reduced the rate of repriming of contracture and this effect of bedpridil was significantly different from that of its quaternary derivative which only showed a significant effect at 10(-5) M. 5. These results demonstrate a clear intracellular effect of bepridil in the ferret heart. Verapamil and CERM 11888 had only weak intracellular effects even at high concentrations. 6. Analysis of the results suggests that the main sites of action of bepridil in this model are the sarcoplasmic reticulum and one or two calcium compartments in the sarcolemma.