ADRENERGIC BLOCKING DRUGS: II. ANTAGONISM OF HISTAMINE AND EPINEPHRINE WITH N-(2-HALOALKYL)-1-NAPHTHALENEMETHYLAMINE DERIVATIVES

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago

Alkyl homologues in a series of N-(2-chloroethyl)-1-naphthalenemethylamines exhibited the remarkable dual property of strongly blocking certain effects of both epinephrine and its physiological antagonist, histamine. The lower alkyl homologues were effective in reducing the toxicity of epinephrine in mice, inducing epinephrine reversal in dogs, reducing toxicity of histamine-aerosol and histamine released during anaphylaxis in guinea pigs, and diminishing depressor responses to injected histamine in dogs.

The most effective compounds were N-(2-chloroethyl)-N-ethyl-1-naphthalenemethylamine (SY-14) and the bromo-analogue (SY-28) which, on a molecular basis were of equal effectiveness in preventing histamine-induced bronchiospasm in guinea pigs and antagonizing epinephrine toxicity in mice. Epinephrine reversal and diminished depressor responses to histamine occurred almost immediately after intravenous injection in dogs and effects were of long duration.

Structure-action relationships are discussed and attention is drawn to similar pharmacological properties of related 2-chloroethylamines under investigation.