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1 Pharmacology Department, School of Medicine, State University of New York at Buffalo, Buffalo, New York
The synergism between the hypnotic effects of chloral hydrate and ethanol was investigated in male mice by determination of ED5O's and use of the isobolographic method. A significant potentiation of the hypnotic effects was observed for mixtures in which these agents were present in a weight ratio equal to or greater than 1:7.2, simple additivity being observed with weight ratios smaller than 1:7.2. Investigation of the synergism between trichloroethanol, an active metabolite of chloral hydrate, and ethanol and chloral hydrate, respectively, revealed no departures from simple additivity, thus leading to the conclusion that the interaction must be one between chloral hydrate and ethanol directly. The potentiation was also characterized by the observations that mixtures with these compositions also exhibited shorter duration of action for equipotent doses and that administration of the ethanol two minutes prior to the chloral hydrate resulted in a further significant potentiation. Synergism of the toxic effects of chloral hydrate and ethanol was investigated by determination of 24-hour, nonaggregated LD5O's. Mixtures of the two agents in the weight ratio 3.6:1 (1:1 molar ratio) revealed significant potentiation, whereas those in the weight ratio of 1:5, 1:10 and 1:15 showed partial but significant antagonism. No departures from simple additivity were seen with mixtures in the weight ratios of 1:1, 1:1.14, 1:3 and 1:30. Therapeutic ratios and standard safety margins for chloral hydrate-ethanol mixtures in the weight ratios of 3.6:1, 1:1 and 1:1.14 were all found to be significantly greater than the respective values for either chloral hydrate or ethanol.
Submitted on September 30, 1968
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