Effects of the MAO inhibitor phenelzine on glutamine and GABA concentrations in rat brain.

Phenelzine (PLZ), a frequently prescribed monoamine oxidase (MAO) inhibitor, is used as an antidepressant/antipanic drug and has been shown to cause marked increases in rat brain levels of the amino acids gamma-aminobutyric acid (GABA) and alanine. In an extension of previous studies related to GABA metabolism, we investigated the effects of PLZ on rat brain levels of glutamine (GLN). At 1, 3 or 6 h after injection of PLZ (15 mg kg-1 i.p.), rats were killed and the brains removed. Analyses (using HPLC with fluorescence detection of OPT derivatives) of whole brain or hypothalamus revealed a decrease in brain levels of GLN and an increase in GABA levels at 3 and 6 h after PLZ injection. The effects of PLZ on GLN and GABA were blocked by prior treatment of the rats with tranylcypromine, a MAO inhibitor that had been shown previously to have no direct effect itself on GABA levels in rat brain. Since PLZ is known to be a substrate (as well as an inhibitor) of MAO, the studies with tranylcypromine pretreatment suggest that the effects on GLN and GABA are caused, at least in part, by a metabolite of PLZ.