Potentiation of the Narcotic Action and Acute Toxicity of Alcohol by Primary Aromatic Monoamines

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Abstract
The interaction with alcohol of several primary aromatic monoamines, occurring naturally in the brain and believed to act as neurohumoral agents, was studied in mice. As much as 3.64 m[image]/kg of serotonin, dopamine, tyramine, and gamma-aminobutyric acid and 1.21 m[image]/kg of tryptamine could be injected intraperitoneally without provoking hypnosis or death; and 0.91 m[image]/kg of each amine could be administered 30 min. before 4.5 gAg of ethanol (a sublethal hypnotic dose) without causing a single death. However, if the animals were given 0.91 m[image]/kg of serotonin, tryptamine or dopamine 30 min. after 4.5 gAg of ethanol, these primary amines induced mortalities of 83, 57 and 50%, respectively, as well as a decisive prolongation in the sleeping time of the survivors. In fact, a dose of only 0.06 m[image]/kg of serotonin, tryptamine or dopamine, which per se provoked little somatic, autonomic or behavioral effects, if given to mice pretreated with alcohol, exhibited a marked potentiation of the latter''s narcotic action. Gamma-aminobutyric acid caused no deaths or increase in the hypnosis period of alcohol-pretreated mice even at a level of 1.82 m[image]/kg while amphetamine actually reduced the sleeping time. The analytical data provided experimental proof that the potentiating effect of the aromatic amines was not attributable either to an increase in the brain alcohol content or to an interference with the over-all rate of alcohol destruction in the body. A tentative mechanism for the metabolic interaction between alcohol and the primary aromatic amines is proposed, and a causal connection is postulated to exist between its neuropharmacological effects, at least in narcotic doses, and its influence on the metabolism of one or more endogenous aromatic monoamines present in the central nervous system.