Mtabaji J P, Manku M S, Horrobin D F
Prostaglandins. 1977 Jul;14(1):125-32. doi: 10.1016/0090-6980(77)90161-7.
Clomipramine inhibited pressor responses to potassium ions and vasopressin in the rat mesenteric vascular bed with an ID50 of about 1.8 microgram/ml against both pressor agents and the actions of indomethacin and PG2 on the clomipramine effect suggested that the drug may have been antagonising the action of an endogenous PG. This was supported by the inhibitory action of clomipramine on PG2 actions on guinea-pig ileum. A lower concentration also inhibited pressor responses to noradrenaline and angiotensin (ID50 about 9 ng/ml): inhibition was increased by PG2 and reduced by indomethacin. In this preparation potassium and vasopressin act primarily by stimulating calcium entry from the extracellular fluid whereas noradrenaline and angiotensin act primarily by releasing calcium from intracellular or membrane-bound stores. Our results can be explained by two actions: 1. a PG-antagonist action of clomipramine at the cell membrane and 2. a selectve inhibitory effect on release of intracellular calcium. Clomipramine may prove useful in studying PG and calcium-dependent mechanisms.
氯米帕明可抑制大鼠肠系膜血管床对钾离子和血管加压素的升压反应，对这两种升压剂的半数抑制浓度（ID50）约为1.8微克/毫升。吲哚美辛和前列腺素E2对氯米帕明作用的影响表明，该药物可能在拮抗内源性前列腺素的作用。这一观点得到了氯米帕明对前列腺素E2作用于豚鼠回肠的抑制作用的支持。较低浓度的氯米帕明也可抑制对去甲肾上腺素和血管紧张素的升压反应（ID50约为9纳克/毫升）：前列腺素E2可增强抑制作用，吲哚美辛则可减弱抑制作用。在该实验制剂中，钾离子和血管加压素主要通过刺激细胞外液中的钙内流起作用，而去甲肾上腺素和血管紧张素主要通过从细胞内或膜结合储存部位释放钙起作用。我们的结果可通过两种作用来解释：1. 氯米帕明在细胞膜上的前列腺素拮抗剂作用；2. 对细胞内钙释放的选择性抑制作用。氯米帕明可能在研究前列腺素和钙依赖性机制方面具有应用价值。
