INHIBITION OF HISTAMINE EFFECTS BY COMPOUNDS OF HISTAMINE, HISTIDINE, AND ARGININE

¹ Instituto Biologico, São Paulo, Brazil

A method of studying quantitatively the anti-histamine effects of histamine, arginine and histidine derivatives upon the isolated guinea pig gut is devised. Among the arginine derivatives studied—benzoyl-l, arginine-amide, benzoyl-l, arginine, hippuryl-nitro, l, arginine and arginine monohydrochloride—the benzoyl-l, arginine-amide was many times more active than arginine monohydrochloride. Since histidine monohydrochloride displayed a similar inhibitory potency, there was assumed that the anti-histamine effect which probably depends on the =NH (imine) group of those amino acid derivatives, attains a maximum corresponding to the anti-histamine effect of benzoyl-l, arginine-amide.

The histamine compounds studied—acetyl-dehydrophenylalanyl-histamine, benzoyl-l, tyrosyl-histamine and acetyl-d, l, phenylalanyl-histamine—are pharmacologically inactive, while still retaining its imine (=NH) group entirely free. They have shown an anti-histamine potency of the order of magnitude of histidine monohydrochloride and benzoyl-l, arginine-amide. The perfect agreement of those results with Ackermann's view that the inhibitory effect of arginine and histidine depends on a competition between the imine group of those amino acids with the like imine group of histamine on its anchoring capacity upon the cellular receptors, is emphasized.

On basis of those quantitative results obtained upon the isolated guinea pig ileum, it was inferred that 0.5 to 1.5 gm. of either arginine or histidine would be enough to counteract the depressor effect of 2 to 5 of histamine base. The experiments performed in the cat gave rather deceiving results. Even when a sufficient excess of arginine or histidine were injected in mixture with small doses of histamine the counteracting effect was small or non-existent. Some times the injection of 1.5 gm. of arginine or histidine in mixture with histamine, produced an aggravation of the effects of the latter.