Actions of the tricyclic antidepressant clomipramine on responses to pressor agents. Interactions with prostaglandin E2

Abstract

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.