Effects of sodium dipropylacetate on .GAMMA.-aminobutyric acid and biogenic amines in rat brain.

Abstract

The effects of sodium dipropylacetate (DPA) on the metabolisms of GABA and biogenic amines in the rat brain were investigated. The results suggested the mechanism of anticonvulsant activity of DPA. The level of GABA in the brain was elevated after oral administration (400 mg/kg). At the peak time (0.5 h), about 45% increase was observed and the elevation of GABA content was maintained for 4 h after administration. In the brain slices, DPA elevated GABA content and suppressed the O2 consumption at 6 mM. DPA had weak inhibitory effects on GABA metabolizing enzymes in brain homogenate. The concentrations of 5-hydroxyindoleacetic acid and tryptophan in the brain were elevated after oral administration of DPA (400 mg/kg). These effects might be caused by the increase of free tryptophan in the serum followed by accelerated incorporation of tryptophan into the brain and the elevated turnover rate of 5-hydroxytryptamine in the brain. DPA elevated the content of dopamine, but the level of norepinephrine was not affected. The changes of these biogenic substances were coincident with the appearance of the anticonvulsant activity of DPA.