EFFECT OF CHAIN LENGTH OF ALIPHATIC AMINES ON HISTAMINE POTENTIATION AND RELEASE

Abstract

Diamines in the series NH_a.(CH₂)_n.NH₂ specifically potentiate histamine contractions of the guinea-pig ileum and inhibit the enzymatic destruction of histamine. These activities are greatest with short-chain compounds (n⋍5). Diamines also release histamine from isolated tissues and depress the contractility of plain muscle and the motility of paramecia. These activities increase with chain-length and are probably limited only by solubility. The parallelism between histamine-releasing activity and toxicity also extends to the monoamines in the series CH₃.(CH₂)_n-1.NH². Histamine-releasing activity of both series increases with increase of pH and can mainly be attributed to the non-ionized base. From the results on the effect of chain-length and ionization on activity, it is suggested that aliphatic amines release histamine by penetration of the cell membrane in the non-ionized form, followed by exchange in the ionic form with intracellular histamine.