苄普地尔、其季铵衍生物CERM 11888和维拉帕米对雪貂心脏咖啡因诱导挛缩的比较作用。

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

Leboeuf J, Leoty C, Lamar J C, Massingham R

Department of Pharmacology, RL-CERM, Riom, France.

Br J Pharmacol. 1989 Sep;98(1):119-26. doi: 10.1111/j.1476-5381.1989.tb16871.x.

Abstract

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.

摘要

比较了苄普地尔、其季铵衍生物CERM 11888（甲基溴化吡咯烷）（10⁻⁷ - 10⁻⁵ M）和维拉帕米（10⁻⁷ - 10⁻⁶ M）对雪貂离体心室小梁咖啡因诱导挛缩的影响。2. 苄普地尔以浓度依赖方式降低挛缩幅度，且该作用与CERM 11888显著不同，CERM 11888与维拉帕米一样，仅在所用最高浓度时降低幅度。3. 苄普地尔（10⁻⁶ M）显著缩短达到峰值张力的时间并加速挛缩的舒张期。后一作用与CERM 11888不同。维拉帕米（10⁻⁶ M）也倾向于加速舒张期。在10⁻⁵ M时，苄普地尔对达到峰值时间和舒张的这些作用趋于逆转。4. 在所有浓度下，苄普地尔和维拉帕米均降低挛缩的再激发速率，苄普地尔的这一作用与其季铵衍生物显著不同，后者仅在10⁻⁵ M时显示出显著作用。5. 这些结果表明苄普地尔在雪貂心脏中有明显的细胞内作用。维拉帕米和CERM 11888即使在高浓度时也仅有微弱的细胞内作用。6. 结果分析表明，在该模型中苄普地尔的主要作用位点是肌浆网和肌膜中的一两个钙池。