Posted by Chairman_MAO on October 7, 2011, at 16:56:24
In reply to Re: Nardil Maintenance Dose » Chairman_MAO, posted by pedr on October 7, 2011, at 8:25:37
Inhibition of GABA-T is not necessarily anxiolytic. It probably is for some people, but it is far more broad-spectrum than "calming"; it's _way_ more complex than that.
Here is the reference:
GABA-elevating effects of the antidepressant/antipanic drug phenelzine in brain: effects of pretreatment with tranylcypromine, (-)-deprenyl and clorgyline
by
Todd KG, Baker GB
Department of Psychiatry,
University of Alberta,
Mackenzie Health Sciences Centre,
Edmonton, Canada.
J Affect Disord 1995 Dec 13; 35(3):125-9ABSTRACT
The antidepressant/antipanic drug phenelzine (PLZ) is both an inhibitor of, and a substrate for, monoamine oxidase (MAO). PLZ also causes an elevation of brain levels of the amino acid neurotransmitter gamma-aminobutyric acid (GABA); this action can be reversed by pretreatment with the MAO inhibitor tranylcypromine (TCP), suggesting that the GABA-elevating effect is largely the result of a metabolite of PLZ formed by MAO. In the present report, rats were pretreated with the nonselective MAO inhibitor TCP, the MAO-A inhibitor clorgyline and the MAO-B inhibitor (-)-deprenyl: at the doses used, clorgyline and (-)-deprenyl caused selective inhibition of MAO-A and MAO-B, respectively. Both TCP and (-)-deprenyl caused a greater reduction in the GABA-elevating action of PLZ than did clorgyline, suggesting that MAO-B is more important than MAO-A in the formation of the active metabolite of PLZ. The results also suggest that an effect other than, or in addition to, inhibition of GABA transaminase by the metabolite may be important in the GABA-elevating action.
1. Biochem Pharmacol. 2002 Jan 1;63(1):57-64.
Effects of the antidepressant/antipanic drug phenelzine and its putative
metabolite phenylethylidenehydrazine on extracellular gamma-aminobutyric acid
levels in the striatum.Parent MB, Master S, Kashlub S, Baker GB.
Department of Psychology, University of Alberta, Edmonton, Canada.
psymbp@langate.gsu.eduPhenelzine (PLZ) is a non-selective monoamine oxidase inhibitor (MAOI) commonly
used to treat depression and panic disorder. As expected, PLZ increases brain
levels of dopamine, norepinephrine, and serotonin. Interestingly, PLZ also
elevates brain levels of gamma-aminobutyric acid (GABA), and previous studies
have suggested that these increases may also contribute to the anxiolytic effects
of PLZ. Using in vivo microdialysis in conscious, freely moving rats, combined
with high performance liquid chromatography, the present experiments determined
that PLZ (15 or 30 mg/kg, free base weight) increases extracellular levels of
GABA in the caudate-putamen and nucleus accumbens. The results also indicated
that phenylethylidenehydrazine (PEH; 29.6 mg/kg, free base weight), a putative
intermediate metabolite of PLZ that is not an MAOI, also significantly increases
extracellular GABA levels in the caudate-putamen. These findings provide further
evidence that GABA may play an important role in the actions of PLZ and suggest
that PEH should be pursued further as a GABAergic drug in its own right.
so, re: your post (a) is an oversimplification or false, (b) that is what GABA-T does, but whether it is bad or good depends upon the patient's needs, (c) It is a metabolite that is a GABA-T inhbiitor (d) yes (e) yes (f) see my answer to (b)
poster:Chairman_MAO
thread:998679
URL: http://www.dr-bob.org/babble/20111006/msgs/999027.html