CHLORAL ALCOHOLATE: REEVALUATION OF ITS ROLE IN THE INTERACTION BETWEEN THE HYPNOTIC EFFECTS OF CHLORAL HYDRATE AND ETHANOL

¹ Pharmacology Department, School of Medicine, State University of New York at Buffalo, Buffalo, New York

The hynotic properties of aqueous solutions of chloral alcoholate were compared in male mice with those of chloral hydrate by determination of ED50's and by sleeping time measurements. It was found that in this species chloral alcoholate is a significantly more potent hypnotic than chloral hydrate, both on a molar and an absolute weight baths. It is also a shorter acting hypnotic than chloral hydrate when equipotent doses are considered. The acute toxicity of aqueous solutions of chloral alcoholate was compared with that of chloral hydrate solutions by determination of the 24-hr, nonaggregated LD50's. It was found that in this same species chloral alcoholate is significantly more toxic on a molar basis than chloral hydrate; nonetheless, chloral alcoholate possesses, in mice, a higher therapeutic ratio and standard safety margin than chloral hydrate. Determination of the osmolality of aqueous solutions of chloral alcoholate leads to the conclusion that the dissociation of chloral alcoholate into chloral hydrate and ethanol is complete within 5 min of dissolution. The hypnotic properties of aqueous chloral alcoholate solutions were found to be indistinguishable from those of an equivalent mixture of chloral hydrate and ethanol.