Effect of valproate on brain GABA: comparison with various medium chain fatty acids

The antiepileptic valproic acid increases brain GABA levels, and interferes with intermediate metabolism. We have therefore evaluated the effects of a number of other medium chain fatty acids on brain GABA. Propionate, isovalerate, pent-4-enoate and diallylacetate all increased whole-brain GABA levels in mice, but only diallylacetate possessed some anticonvulsant activity. Hyperammonaemia is a common side effect observed with these acids, but artificially induced hyperammonaemia through injections of ammonium chloride did not alter brain GABA. These results suggest that high doses of valproate may increase brain GABA by interfering with intermediate metabolism, possibly at the level of medium chain acyl CoA. However alterations in brain GABA did not correlate with anticonvulsant activity.