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.
Paslawski
T M
TM
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Sloley
B D
BD
Baker
G B
GB
D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry; D005973:Glutamine / Q000032:analysis*; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D008996:Monoamine Oxidase Inhibitors; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D010624:Phenelzine