Cortijo J, Foster R W, Small R C, Morcillo E J
Departamento de Farmacologia y Farmacotecnia, Facultat de Medicina, Universitat de València, Spain.
J Pharm Pharmacol. 1990 Jun;42(6):405-11. doi: 10.1111/j.2042-7158.1990.tb06580.x.
In guinea-pig trachealis, depolarized by a K(+)-rich medium, Ca2+ (0.01-10 mM) caused concentration-related spasm. Verapamil (0.5-5 microM), cinnarizine (10-100 microM) and trifluoperazine (16-160 microM) each produced concentration-dependent antagonism of Ca2+ characterized by a rightward and downward displacement of the log concentration-effect curve for Ca2+. The rank order of potencies of these antagonists, measured as the IC75 against Ca2+ (10 mM)-induced contraction of depolarized trachea, was verapamil (5.6 microM) greater than cinnarizine (59 microM) greater than trifluoperazine (91 microM). In skinned trachea, verapamil in concentrations up to 100 microM did not modify the concentration-effect curve for Ca2+. In contrast, cinnarizine (59-177 microM) diminished the sensitivity and trifluoperazine (273 microM) decreased the responsiveness of the tissue to Ca2+. In skinned trachea, trifluoperazine (91 microM) produced greater inhibition of Ca2+ (10 microM)-induced contraction after 120 min than after 30 min of incubation. Verapamil (100 microM) and cinnarizine (177 microM) were devoid of inhibitory effect against the 10 microM Ca2+ standard. In skinned trachea, changes in the Ca2+ concentration-effect curve produced by cinnarizine (177 microM) were reversed after washout whilst those induced by trifluoperazine (273 microM) persisted. It is concluded that distinct differences exist between the three calcium antagonists examined. The action of verapamil is restricted to the plasmalemma. That of cinnarizine and trifluoperazine is exerted both on the plasma membrane and upon the intracellular contractile machinery.
在富含钾的培养基中去极化的豚鼠气管条上，Ca2+（0.01 - 10 mM）引起浓度相关的痉挛。维拉帕米（0.5 - 5 microM）、桂利嗪（10 - 100 microM）和三氟拉嗪（16 - 160 microM）各自产生对Ca2+的浓度依赖性拮抗作用，其特征为Ca2+的对数浓度 - 效应曲线向右下方移位。这些拮抗剂的效价顺序，以对去极化气管条上Ca2+（10 mM）诱导收缩的IC75来衡量，为维拉帕米（5.6 microM）大于桂利嗪（59 microM）大于三氟拉嗪（91 microM）。在脱细胞气管条中，高达100 microM浓度的维拉帕米并未改变Ca2+的浓度 - 效应曲线。相反，桂利嗪（59 - 177 microM）降低了敏感性，三氟拉嗪（273 microM）降低了组织对Ca2+的反应性。在脱细胞气管条中，孵育120分钟后，三氟拉嗪（91 microM）对Ca2+（10 microM）诱导收缩的抑制作用比孵育30分钟后更大。维拉帕米（100 microM）和桂利嗪（177 microM）对10 microM Ca2+标准无抑制作用。在脱细胞气管条中，冲洗后桂利嗪（177 microM）产生的Ca2+浓度 - 效应曲线变化可逆转，而三氟拉嗪（273 microM）诱导的变化持续存在。结论是，所研究的三种钙拮抗剂之间存在明显差异。维拉帕米的作用局限于质膜。桂利嗪和三氟拉嗪的作用既作用于质膜，也作用于细胞内收缩机制。
