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Re: +++ MAO-A or B ? Gerovital (procaine) selectivity Marty

Posted by SLS on July 3, 2008, at 5:34:15

In reply to Re: +++ MAO-A or B ? Gerovital (procaine) selectivity SLS, posted by Marty on June 29, 2008, at 11:14:41

I feel strongly that MAO-A is the main player in mood disorders.

Investigations into the gene activity that expresses MAO-A in depressed subjects has been demonstrated to be reduced. Results of genotyping have recently implicated the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR) as being underexpressed.

Moclobemide is a great example of how a selective inhibitor of MAO-A can produce a robust remission of depression, even if only transiently. I would assign the reason for the tachyphylaxis that is commonly seen with moclobemide as its being reversible.

Selegiline does not seem to be nearly as potent as Nardil or Parnate when treating severe depression, as the reported experiences on PB give an indicator to. My guess is that there is indeed some MAO-A inhibition with selegiline at the dosages necessary to treat depression. I would want to research that a bit before calling this a fact. The risk of tyramine reaction increases with dosage. Investigators warn of this when discussing hypertensive crisis, such that it is recommended to not ingest tyramine at any dosage above the minimum of 6mg/24hr. This would be an indicator that selegiline inhibits MAO-A in the gut.

I wouldn't be afraid of MAO-A inhibitors. Just be afraid of moclobemide. It can elicit intense depressive reactions in some people that I don't believe is due to MAO inhibition. I remember reading that it can deplete dopamine, but I don't remember how.

"Conclusions: STS [selegiline transdermal], an monoamine oxidase inhibitor antidepressant that potentiates the three major monoamine neurotransmitters (serotonin, norepinephrine, and dopamine)"

- Scott


1: Psychopharmacol Bull. 2007;40(3):15-28.Links
Treatment effects of selegiline transdermal system on symptoms of major depressive disorder: a meta-analysis of short-term, placebo-controlled, efficacy trials.
Robinson DS, Gilmor ML, Yang Y, Moonsammy G, Azzaro AJ, Oren DA, Campbell BJ.

Worldwide Drug Development, Burlington, VT.

Objective: Selegiline transdermal system (STS) is efficacious for the treatment of major depressive disorder (MDD). This meta-analysis explores treatment effects of STS for individual symptoms of MDD derived from line-item analyses of the 28-item Hamilton Rating Scale for Depression (HAM-D28) and the Montgomery-Asberg Depression Rating Scale (MADRS). Methods: Change in score from baseline to end of treatment for each item of the HAM-D28 and MADRS was assessed using a multilevel model for meta-analysis of continuous outcome data from all five short-term, randomized, placebo-controlled efficacy trials conducted during preapproval clinical development of STS for MDD. Utilizing a random-effects model with trial effects fixed and adjusting for baseline scores, confidence intervals (95%) were computed for treatment differences between STS and placebo. Results: STS exhibited significant treatment effects on core depression symptoms (HAM-D Bech-6 items: depressed mood, guilt, work and activities, retardation, psychic anxiety, general somatic symptoms), reverse vegetative symptoms (oversleeping, overeating), motoric retardation, suicide, and genital symptoms (libido). Significant STS treatment effects were also noted for each MADRS item except for reduced sleep and appetite. The most prominent MADRS effects were improvement in sadness, lassitude, and poor concentration. Conclusions: STS, an monoamine oxidase inhibitor antidepressant that potentiates the three major monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), has beneficial therapeutic effects for a spectrum of individual symptoms rated by the HAM-D28 and MADRS. Analyses of specific symptoms assessed by depression rating scales can offer guidance to clinicians in individualizing drug therapy based on presenting symptoms.





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