Possible Interaction: Gamma-Aminobutyric Acid and Isoniazid

“Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (+/- S.E.M.) levels of gamma-aminobutyric acid , aspartate, asparagine, homocarnosine, ornithine, histidine, alpha-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of beta-alanine in both CSF and plasma.”

“The results showed that the GABA concentrations in CSF tripled following treatment with isoniazid although no significant change occurred in plasma GABA levels.”

“Because INH inhibits the enzyme y-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease.”

“It was found that that (16.6±10.2)% of the supposed GABA signal originated from homocarnosine, and that isoniazid caused significantly elevated concentration of GABA and homocarnosine in a single subject compared to controls.”

“ INH inhibits this enzymatic pathway causing a decrease in brain levels of GABA , the major inhibitory neurotransmitter in the central nervous system, with resultant increase in susceptibility to seizures.”

“Furthermore, isoniazid produces an initial decrease in brain GABA followed by a subsequent increase to twice the normal levels (5) .”

“ Isoniazid is well known to increase the concentrations of γ-aminobutyric acid in neural tissues.”

“CSF GABA concentrations increased markedly during isoniazid administration, presumably reflecting increases in brain GABA content.”

“The results indicate that while total GABAergic peptides are not altered in several of the neurologic diseases studied, drugs such as isoniazid and/or pyridoxine can significantly elevate both free and conjugated GABA levels in human CSF.”

“The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side.”