The effect of harmaline and related harmala alkaloids on ouabain-stimulated contractions of the guinea-pig ileum.

Harmaline, harmine, 2-methylharmine and harmolol, members of the harmala family of alkaloids were tested for their action on ouabain-elicited contractions of the guinea-pig ileum. All four alkaloids were found to relax tissue previously contracted by ouabain, but they differed in their potency and reversibility. Harmaline was equipotent with harmine but more easily reversible. 2-Methylharmine and harmolol were found to be less potent and readily reversible. It is evident that the inhibition mediated by harmaline occurs at a site other than that which ouabain binds. Ca-free Tyrode caused relaxation of tissue contracted by ouabain. This effect was partially reversed in the presence of normal Tyrode solution. In presence of high K the response to ouabain was almost abolished. Harmaline inhibited Ca-induced contractions in a non-competitive manner while neither 2-methylharmine nor harmalol had any effect. In the discussion the action of harmala alkaloids is shown to be directly related with CA ion movements.