Isopropyl substitution on barbiturate ring: effects on 'open field' and 'hole board' behaviour and on biogenic amines concentrations in discrete regions of the rat brain after acute and chronic administration.

Abstract

Previous studies have shown that slight modification of the barbitone molecule can lead to enhanced sedative activity, convulsant activity or putative antidepressant activity according to the position of the isopropyl substituent on the N- or O-moiety. When the acute effects of the N-, O2- and O4-isopropyl derivatives of barbital (NIB, O2IB), O4IB on the concentrations of brain biogenic amines were determined, it was found that NIB and O4IB increased the serotonin concentrations in several brain regions examined without markedly changing the 5-hydroxy-indole acetic acid (5-HIAA) concentrations; in contrast, O2IB increased the 5-HIAA concentration. Barbitone and NIB raised the concentration of noradrenaline in two of the regions examined whereas the O2-substituted derivative had a smaller effect; the dopamine concentration was slightly raised by NIB and O2IB. Following their chronic (14 days) administration, only barbitone and O2IB raised the serotonin concentration; O2IB raised the concentration of 5-HIAA in some regions as did NIB, which suggests that these compounds may increase serotonin turnover. Barbitone and O2IB slightly increased the noradrenaline content of the brain stem while only O2IB decreased the dopamine content. These results suggest that the effects of acute and chronic administration of barbitone and its isopropyl derivatives are qualitatively different; their effects are less marked after chronic administration. The GABA concentration was only affected after chronic administration, when NIB was shown to increase and O2IB to decrease the concentration. Following their chronic administration, O2IB decreased while NIB increased the locomotor activity of rats in the 'open field' and 'hole board' apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)