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

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.