Milovanović S R, Varagić V M
Arch Int Pharmacodyn Ther. 1987 May;287(1):158-68.
Increasing concentrations of fendiline inhibit various types of muscle activation (KCl, oxytocin and electrical stimulation), as well as spontaneous rhythmic activity of the isolated uterus of the rat. Contrary to verapamil and nifedipine, fendiline in micromolar concentrations (from 1.5 to 15.5 mumol) affects various types of muscle activation almost to the same degree. Fendiline probably influences a common pathway in calcium metabolism in all types of muscle activation. The relaxant effect of fendiline does not depend on cAMP, being even associated with a significant decrease of the level of this nucleotide during electrical stimulation of the isolated uterus of the rat. Fendiline may have its place in the therapy of premature delivery and abortion, particularly because it exhibits lower selectivity in relation to the type of activation of the smooth muscle. Fendiline induces a stronger inhibition of the tonic than of the phasic component of contraction produced by oxytocin and KCl. Fendiline is more active against the oxytocin-induced contraction, probably due to an additional action on the fast Na+ channels. These findings indicate that KCl and oxytocin act through different calcium channels (voltage and receptor calcium channels). Our experiments in which fendiline inhibited more strongly the tonic than the phasic component of KCl-produced contraction also confirm the hypothesis on the existence of voltage calcium channels (or subtypes of one voltage calcium channel) in the isolated uterus of the rat. By adding calcium to the medium, almost all types of muscle activation are established, after the inhibitory action of fendiline, except its depressive action on the electrical stimulation of the isolated rat uterus. Calcium most effectively antagonizes the inhibitory effect of fendiline on spontaneous rhythmic activity. The finding that certain types of activation, after the inhibitory action of fendiline, occur to a different degree by addition of calcium to the medium, are also indirect confirmation of the existence of different calcium channels. Halothane, in a concentration of 1 vol %, did not change the relaxant action of fendiline during electrical stimulation and during spontaneous rhythmic activity.
芬地林浓度增加会抑制各种类型的肌肉激活（氯化钾、催产素和电刺激）以及大鼠离体子宫的自发节律活动。与维拉帕米和硝苯地平相反，微摩尔浓度（1.5至15.5微摩尔）的芬地林对各种类型的肌肉激活影响程度几乎相同。芬地林可能影响所有类型肌肉激活中钙代谢的共同途径。芬地林的松弛作用不依赖于环磷酸腺苷（cAMP），甚至在大鼠离体子宫电刺激期间与该核苷酸水平的显著降低有关。芬地林可能在早产和流产治疗中占有一席之地，特别是因为它对平滑肌激活类型的选择性较低。芬地林对催产素和氯化钾引起的收缩的强直成分的抑制作用比对相性成分的抑制作用更强。芬地林对催产素诱导的收缩作用更强，可能是由于对快速钠通道有额外作用。这些发现表明氯化钾和催产素通过不同的钙通道（电压门控钙通道和受体操纵性钙通道）起作用。我们的实验中，芬地林对氯化钾引起的收缩的强直成分的抑制作用比对相性成分更强，这也证实了大鼠离体子宫中存在电压门控钙通道（或一种电压门控钙通道的亚型）的假说。通过向培养基中添加钙，在芬地林的抑制作用后，几乎所有类型的肌肉激活都得以恢复，但芬地林对大鼠离体子宫电刺激仍有抑制作用。钙最有效地拮抗芬地林对自发节律活动的抑制作用。在芬地林的抑制作用后，通过向培养基中添加钙，某些类型的激活以不同程度恢复，这一发现也间接证实了不同钙通道的存在。1%体积浓度的氟烷在电刺激和自发节律活动期间未改变芬地林的松弛作用。
