Neuropharmacological effects induced by butanol, 4-hydroxybutyrate, 4-mercaptobutyric acid thiolactone, tetrahydrofuran, pyrrolidine, 2-deoxy- d-glucose and related substances in the rat

Abstract

The present study evaluated in the rat the gross behavioural and electroencephalographic activity produced by several short chain aliphatic alcohols, fatty acids, some of their derivatives and some heterocyclic 5-ring compounds that have structural similarities mainly to 4-hydroxybutyric acid and butyrolactone. 4-Hydroxybutyric acid (and butyrolactone) produced a progression of EEG and behavioural changes characteristic of generalized non-convulsive epilepsy. During the period of continuous EEG high amplitude slow wave activity, the rat was cataleptoid and during periods of spiking with electrical silence, the righting reflex was lost. Non-convulsive epileptoid activity with some characteristics similar to that produced by 4-hydroxybutyric acid and butyrolactone was observed following administration of butanol, 2-butanol, 1,4-butane-diol, 4-chlorobutanol, 4-methoxybutyric acid, 4-chlorobutyric acid, tetrahydrofuran and 2-deoxy- d-glucose. Convulsive seizures were observed following 4-mercaptobutyric acid thiolactone and pyrrolidine. The results are discussed with regard to the structural components necessary to elicit epileptoid activity and the possible mechanism of action. It is suggested that part of the mechanism of action of these substances may involve inhibition of the enzymes involved in brain glutamate and aspartate metabolism.