Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia

Abstract

To investigate the role of GABA-ergic systems in parkinsonism, sodium valproate, an inhibitor of GABA catabolism, was administered to eight parkinsonian patients in a double blind, placebo controlled trial. Maximum daily doses of valproate ranged from 27 to 62 mg/kg. Parkinsonism scores were not significantly altered by valproate treatment although bradykinesia sub-scores tended to increase. L-DOPA induced dyskinesia were increased in four of the five patients with this problem and required a reduction of L-DOPA in three. Plasma L-DOPA concentrations were not influenced by valproate treatment suggesting that the enhancement of dyskinesias was not a result of alteration of peripheral L-DOPA metabolism. In six patients cerebrospinal fluid (CSF) GABA was measured by a radioreceptor assay during the placebo and the high dose valproate phases of the study. Valproate had no consistent effect on the concentration of GABA in the CSF. These results suggest that sodium valproate is of no clinical benefit in the treatment of parkinsonism or L-DOPA induced dyskinesia. Although proof that valproate augmented GABA-ergic neurotransmission is lacking, the increase of bradykinesia and L-DOPA induced dyskinesia is consonant with recent animal studies in which GABA-mimetics decreased locomotion but facilitated stereotypy induced by dopaminergic agents.