Suppression of the ethanol withdrawal syndrome by aliphatic diols

Considerable evidence both in vitro and in vivo suggests that alcohols exert their intoxicating properties through an interaction with membranes. A wide range of alcohols and diols with divergent structures induce a virtually identical spectrum of intoxication signs. Because of their pharmacological similarities to ethanol, a number of aliphatic diols were tested to determine whether this class of compounds may have efficacy in suppressing the ethanol withdrawal syndrome in rats. All of the diols tested, when administered intragastrically, were effective without inducing intoxication. Furthermore, the withdrawal-suppressing potencies of these drugs were related to their ability to partition into membranes, the same property that determines their potency as depressants. Two halogenated hydrocarbons, which are amphiphiles like alcohols and diols, were both able to suppress the withdrawal syndrome, although several aliphatic hydrocarbons could not. The data suggest that short-chain aliphatic alcohols and diols may have a common site of action, possibly in a region in membranes near the aqueous membrane interphase.