Rehavi M, Carmi R, Weizman A
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Eur J Pharmacol. 1988 Oct 11;155(1-2):1-9. doi: 10.1016/0014-2999(88)90396-2.
The activity of various calcium channel blockers at the serotonin transporter, as determined by their effects on imipramine binding and serotonin uptake, was investigated in rat brain and human platelets. In addition, the effect of tricyclic antidepressants on the binding of calcium channel blockers was evaluated. Verapamil was found to be a competitive inhibitor of both imipramine binding and serotonin uptake in brain and platelets. The inhibitory activity of verapamil was calcium-independent. Chronic verapamil treatment resulted in a significant decrease (28%) in [3H]imipramine binding in the rat hypothalamus but had no effect on [3H]imipramine binding to cerebral cortex membranes or on [3H]serotonin uptake in these two brain regions. Tricyclic antidepressants inhibited (-)-[3H]desmethoxyverapamil binding but did not affect [3H]nitrendipine binding to rat cerebral cortex membranes. Chronic imipramine treatment induced a non-significant increase (34%) in (-)-[3H]desmethoxyverapamil binding but did not alter [3H]nitrendipine binding in rat cerebral cortex. These interactions may be relevant to an understanding of the beneficial effects of verapamil in major affective disorders and may suggest an involvement of calcium channels in the pharmacological activity of tricyclic antidepressants.
通过观察各种钙通道阻滞剂对丙咪嗪结合及血清素摄取的影响，研究了它们在大鼠脑和人血小板中血清素转运体上的活性。此外，还评估了三环类抗抑郁药对钙通道阻滞剂结合的影响。发现维拉帕米是脑和血小板中丙咪嗪结合及血清素摄取的竞争性抑制剂。维拉帕米的抑制活性与钙无关。慢性维拉帕米治疗导致大鼠下丘脑[3H]丙咪嗪结合显著减少（28%），但对这两个脑区的大脑皮质膜[3H]丙咪嗪结合或[3H]血清素摄取无影响。三环类抗抑郁药抑制（-）-[3H]去甲氧基维拉帕米结合，但不影响[3H]尼群地平与大鼠大脑皮质膜的结合。慢性丙咪嗪治疗使大鼠大脑皮质中（-）-[3H]去甲氧基维拉帕米结合有非显著性增加（34%），但不改变[3H]尼群地平结合。这些相互作用可能与理解维拉帕米在主要情感障碍中的有益作用相关，并可能提示钙通道参与三环类抗抑郁药的药理活性。
