Johnson J D, Fugman D A
J Pharmacol Exp Ther. 1983 Aug;226(2):330-4.
Ca++ antagonist drugs (also known as Ca++ channel blockers) and the calmodulin antagonists trifluoperazine (TFP) and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were capable of half-maximally relaxing porcine coronary segments at 1.5 X 10(-10) M for felodipine, 6.5 X 10(-8) M for verapamil, 2.6 X 10(-7) M for diltiazem, 7 X 10(-7) M for prenylamine, 7 X 10(-6) M for TFP and 45 X 10(-6) M for W-7. Their correspondent binding to calmodulin was half-maximal at 2.8 X 10(-6), 30 X 10(-6), 80 X 10(-6), 5 X 10(-7), 5.0 X 10(-6) and 11 X 10(-6) M, respectively. Only prenylamine, TFP and W-7 were capable of relaxing coronaries over the same concentration range in which they bind to calmodulin. The relaxations produced by these calmodulin antagonists and prenylamine could not be overcome by contractile agonists which release Ca++ from internal stores (histamine and serotonin), whereas the relaxations produced by felodipine, verapamil and diltiazem were readily reversed by either of these agonists. This is consistent with TFP and W-7 and to some degree prenylamine-inducing vasodilation by calmodulin antagonism and with felodipine, verapamil and diltiazem vasodilating through Ca++ antagonism of Ca++ channels at the level of the cell membrane.
钙离子拮抗剂药物（也称为钙通道阻滞剂）以及钙调蛋白拮抗剂三氟拉嗪（TFP）和W - 7 [N -（6 - 氨基己基）- 5 - 氯 - 1 - 萘磺酰胺]能够使猪冠状动脉节段产生半数最大舒张效应，其中非洛地平的浓度为1.5×10⁻¹⁰ M，维拉帕米为6.5×10⁻⁸ M，地尔硫䓬为2.6×10⁻⁷ M，普尼拉明为7×10⁻⁷ M，TFP为7×10⁻⁶ M，W - 7为45×10⁻⁶ M。它们与钙调蛋白的相应结合半数最大效应浓度分别为2.8×10⁻⁶、30×10⁻⁶、80×10⁻⁶、5×10⁻⁷、5.0×10⁻⁶和11×10⁻⁶ M。只有普尼拉明、TFP和W - 7在与钙调蛋白结合的相同浓度范围内能够使冠状动脉舒张。这些钙调蛋白拮抗剂和普尼拉明所产生的舒张作用不能被从细胞内储存释放钙离子的收缩性激动剂（组胺和5 - 羟色胺）所克服，而由非洛地平、维拉帕米和地尔硫䓬所产生的舒张作用则很容易被这两种激动剂中的任何一种所逆转。这与TFP和W - 7以及在某种程度上普尼拉明通过钙调蛋白拮抗作用诱导血管舒张是一致的，并且与非洛地平、维拉帕米和地尔硫䓬通过在细胞膜水平对钙通道的钙离子拮抗作用而使血管舒张也是一致的。
