Elsevier

Neuropharmacology

Volume 17, Issue 7, July 1978, Pages 451-461
Neuropharmacology

Physico-chemical correlates of alcohol intoxication

https://doi.org/10.1016/0028-3908(78)90050-3Get rights and content

Abstract

In previous attempts to determine the molecular basis of action of alcohols and other depressants, experiments have generally been performed in vitro with artificial systems or were concerned only with narcotizing properties. The main medical concern with alcohols, especially ethanol, is their ability to induce intoxication, involving impairment of gait, slowed reflexes, muscular flaccidity and impaired judgment. No attempts have been made previously to gain an estimate of some of the molecular properties of alcohols using well-defined behavioural endpoints in vivo. In the present study, over 60 compounds, including monohydroxyl alkanols, dihydroxy alkanols, cyclic alcohols and diols and others were tested for their ability to induce pronounced ataxia in rats. The effective dose necessary to produce the desired behavioural endpoint was compared to their membrane/buffer partition coefficient, concentration in the non-aqueous phase of the animal, volume of the non-aqueous phase occupied, and thermodynamic activity. Nearly all the compounds tested induced a behavioural spectrum of intoxication virtually identical to that of ethanol. Furthermore, there was a high inverse correlation between the effective dose that induced ataxia and the membrane/buffer partition coefficient up to a certain carbon number. On the other hand, no correlation was found with the other three parameters. Intoxication was also observed with non-alcoholic, aliphatic amphiphiles such as propylchloride and propanethiol, but not with the pure hydrocarbons pentane or hexane.

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