Clinical and biochemical effects of gamma-vinyl Gaba

SUMMARY Clinical and biochemical effects of Gamma-vinyl-Gaba (GVG) have been evaluated in a blind video-controlled study in 10 psychiatric patients (mean age 71 yr) with tardive dyskinesia. CSF free and total Gaba and homocarnosine concentrations increased from three to five fold with GVG treatment. Despite the GVG-induced biological effects on Gaba metabolism, GVG did not consistently improve tardive dyskinesia. Psychomotor side-effects occurred in older patients, who only tolerated GVG dosages of 2-4 g/day. Tardive dyskinesia, a neurological disorder of abnor-mal hyperkinetic movement, is a frequent side effect of chronic administration of neuroleptic treatment.1 It occurs in predisposed patients, in whom it may become a persistent problem for which no entirely satisfactory treatment is known.2 The patho-physiology of tardive dyskinesia has not been definitively elucidated but the most widely accepted hypothesis is the development of dopamine receptor hypersensitivity of the striatum following prolonged exposure to neuroleptics. ' 3 In chronically neu-roleptic treated laboratory animals, the co-administration of Gabaergic agonists has been shown to prevent the occurrence of apomorphine-induced stereotypes4 and to inhibit neuronal dopaminergic activity. ' Therefore Gabaergic agonists might be effective agents to treat tardive dyskinesia in humans. Clinical trials using drugs with putative Gabaergic activity have produced mixed results. Thus, sodium valproate6 and baclofen7 have been claimed to be slightly beneficial. Muscimol8 and y-acetylenic Gaba9 were also moderately effective but at the expense of unacceptable side effects. THIP was ineffective in tardive dyskinesia, with high doses being poorly tolerated. '