Potentiation of the Action of Histamine by Semicarbazide

Abstract

ZELLER¹ has shown that semicarbazide inhibits histaminase. We have found that this substance, added to Tyrode solution, potentiates the action of histamine on the guinea pig's ileum. The lowest concentration at which semicarbazide clearly potentiates histamine is of the order of 10⁻⁹. The optimum concentration is approximately 10⁻⁶, when the size of the histamine contractions may be doubled. Very high concentrations depress the effects of histamine. Potentiation is rapidly established and readily reversible. The accompanying record shows that semicarbazide selectively potentiates histamine, but has no similar effect on acetylcholine. Semicarbazide alone produces no contraction of the ileum, and the potentiation is probably due to inhibition of histaminase. Eserine, which inhibits, cholinesterase, potentiates the effect of acetylcholine on the ileum much more than that of histamine. Certain other inhibitors of histaminase also potentiate histamine. The most active compound hitherto found is 2-methyl-5-amino-methyl-6-amino-pyrimidine (B₁ pyrimidine) which we have obtained through the kindness of Dr. Bergel, of Roche Products, Ltd. This compound potentiates histamine in a concentration of 2 × 10⁻¹⁰.