Effect of 1,4-butanediol and other butyric acid congeners on brain catecholamines

Abstract

Many butyric acid congeners were screened for their behavioural effect and for their influence on brain amines. Among the compounds examined, all butyric acid derivatives endowed with depressant action on the CNS, and only those endowed with such action, were capable of increasing selectively brain DA. Brain NE and serotonin were not influenced. Besides ▪-OH and ▪-BL, the following compounds were found to be active: 1,4-BD, α-OH-butyric acid, ▪-BL- ▪-carboxylic acid and succinate. 1,4-BD was studied in detail in rats and in rabbits. The effect of this compound shows close similiarities to that of ▪-OH. There is a direct correlation between the degree of sedation produced by this compound an the accumulation of DA in the brain. This is particularly evident in rabbits: the anaesthetic effect occurs after a delay of about two hours, as does the rise in brain DA. The DA levels return to normal when the animals are awake. The newly-formed DA is localized in the pallidum and in the striatum. The mechanism by which the above compounds, and specifically 1,4-BD, produce the change in brain DA is not clear: 1,4-BD, like ▪-OH, does not inhibit MAO either in vivo or in vitro. The fact that 1,4-BD produces its effect after a long delay suggests that it acts through an active metabolite.