Elevation of brain GABA content by chronic low-dosage administration of hydrazine, a metabolite of isoniazid.

摘要: When gamma-aminobutyric acid aminotransferase (GABA-T) activity was measured in vitro rat brain, neither isoniazid (INH) nor for of its known metabolites (isonicotinic acid, acetylisoniazid, acetylhydrazine, diacetylhydrazine) inhibited the enzyme concentrations (5 mM) far higher than those likely to be achieved when INH is administered man. In contrast, hydrazine micrometers) caused a 50% inhibition GABA-T without inhibiting glutamic decarboxylase (GAD). Rats were injected daily 109 days with (0.08 or 0.16 mmol/kg/day), after which amino contents and activities their brains. Both doses significant elevations whole brain GABA content reductions activity, but did not affect GAD activity. Chronic administration at these reduce weight gain alter behavior, it produce any irreversible pathologic changes liver alterations hepatic aryl hydrocarbon hydroxylase However, treatment many acids besides GABA, markedly increased ornithine, tyrosine, alpha-aminoadipic plasma. Inhibition other biochemical observed patients given high probably result from formed metabolic degradation INH. Thus might more direct means elevating where this seems indicated, entail greater risk adverse effects.