Brain amino compounds in a Huntington's disease patient on isoniazid therapy

We describe biochemical abnormalities in autopsied brain of a patient with early Huntington's disease (HD) who died of pentobarbital overdosage while under treatment with isoniazid (INH). The brain contained hydrazine, a terminal metabolite of INH, which inhibits gamma-aminobutyric acid (GABA) aminotransferase. GABA content in the basal ganglia was higher than expected for HD, and GABA content was supranormal in some brain regions. Homocarnosine (GABA-histidine) content was greatly elevated in all brain regions, suggesting chronic GABA elevation in life. Therefore, the increase in brain GABA content observed in experimental animals given INH or hydrazine also occurs in human patients.