Effects of the antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain.
The effects of long-term (28-day) administration of several antidepressant/antipanic drugs [imipramine, desipramine, tranylcypromine and phenelzine (PLZ)] on gamma-aminobutyric acid-tranaminase (GABA-T) activity and GABA levels were investigated in rat frontal cortex. Of the drugs investigated, only PLZ inhibited GABA-T and elevated GABA levels. Additional short-term experiments were conducted with PLZ, and they demonstrated a dose-dependent inhibition of GABA-T in rat whole brain. Time-response studies on inhibition of GABA-T in whole brain demonstrated that at a dose of PLZ of 15 mg/kg i.p. inhibition of GABA-T remained relatively constant from 1 to 8 hr and that the enzyme was still inhibited by 23% at 24 hr after PLZ administration.
McManus
D J
DJ
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Martin
I L
IL
Greenshaw
A J
AJ
McKenna
K F
KF
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D010200:Panic / Q000187:drug effects*; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014191:Tranylcypromine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D000928:Antidepressive Agents; D014191:Tranylcypromine; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D010624:Phenelzine; D007099:Imipramine; D003891:Desipramine