Van Nueten J M, Van Beek J, Janssen P A
Arzneimittelforschung. 1978;28(11):2082-7.
Flunarizine, a difluoro derivative of cinnarizine, produces a long-lasting inhibition of calcium-induced contractions of isolated vascular preparations of rabbit and rat. In this regard it is slightly more active than cinnarizine and markedly more active than papaverine, naftidrofuryl, bencyclane, cylandelate, dihydroergotoxine, xantinol nicotinate and pentoxifylline; calcium dobesilate does not inhibit the calcium-induced responses. A long-lasting antivasoconstrictor effect was observed also for cinnarizine. This action of flunarizine is selective for calcium channels in vascular tissue, since it has little effect on the calcium-induced response of myocardial preparations of the cat. Flunarizine has no effect on the rhythmic activity of myogenically active blood vessels; it thus shows a further selective activity to calcium channels activated by vasoconstrictor agents and not for those opened by intrinsic changes in membrane permeability. This dual selectivity implies that flunarizine is a useful reference substance in assessing calcium antagonism.
氟桂利嗪是桂利嗪的二氟衍生物,能对兔和大鼠离体血管制剂的钙诱导收缩产生持久抑制作用。在这方面,它比桂利嗪活性略高,比罂粟碱、萘呋胺酯、苄环烷、环扁桃酯、双氢麦角毒碱、烟酸占替诺和己酮可可碱活性明显更高;二盐酸半胱氨酸钙不抑制钙诱导反应。桂利嗪也观察到持久的抗血管收缩作用。氟桂利嗪的这一作用对血管组织中的钙通道具有选择性,因为它对猫心肌制剂的钙诱导反应几乎没有影响。氟桂利嗪对肌源性活性血管的节律性活动没有影响;因此,它对血管收缩剂激活的钙通道表现出进一步的选择性活性,而对膜通透性内在变化打开的钙通道则无此作用。这种双重选择性意味着氟桂利嗪是评估钙拮抗作用的有用参考物质。