Posted by Scott L. Schofield on November 25, 1999, at 12:06:04
In reply to Re: moclobemide, posted by Roberto Muehlenkamp on November 19, 1999, at 11:57:42
> > > I started taking Moclobemide about a month ago (first
> > > 300 mg, then 450 mg. Everything went down the drain.
> > > Not only did the depression not improve, it became a lot worse.
> >
> > > Has anyone experienced anything similar? I would very much like to know that
> > > I'm not the only one who cannot take this drug.
> >
> >
> > Yes !!!
> >
> > I thought I was the only one to experience this. I didn't want to post anything about it as not to dissuade anyone from trying it. Moclobemide made me feel worse than I ever have before of since. Thank God it has such a short half-live. Things got better within two days after discontinuation.
> >
> > I have one thought as to why it happened. I came across an abstract which concluded that moclobemide causes depletion of dopamine stores in certain areas of the brain. I don't remember which ones, but I believe they were limbic. I may go back to see if I can find it. For a long time I have suspected that my particular illness involves dopamine activity. This paper added another log to the fire.
> >
> >
> > Thanks a lot for the post.
> > I'm relieved to know that I wasn't the only one.
> >
> >
>
> I found something that may go in the direction of your theory:
> MOCLOBEMIDE
> Humans now have the capacity to choose their own individual level of activity or inhibition of
> the two primary monoamine oxidases. This does not quite enable the fine-tuning of
> personality variables with the functional equivalent of a graphic equaliser. It still represents
> a promising start. In MAO-inhibition, as in life, more is not always better. Excessive
> dosages of l-deprenyl intake, for instance, may actually shorten, not increase, life expectancy
> - at least in Parkinsonians if it's combined with l-dopa. And levels of above 80% inhibition of
> MAO-A may lead to a sharp and possibly unwanted fall in dopamine synthesis. Repairing
> Nature's niggardliness will be a priority for the decades ahead.
> Source: http://www.neuropharmacology.com/
>
> By the way: As this source quotes Moclobemide as having been called the "gentle MAOI", I sent them my experience report. Maybe they'll reconsider on this qualification.
>
> If you find your source, please let me know.
>
> Kind regards,
> Roberto
Hi Roberto.
Here are a couple of studies involving the changes that moclobemide may have on dopamine activity. I know it's a bit of a mental leap, but perhaps the increased release of dopapine without any compensatory blockade of MAO-B eventually leads to dopamine depletion. Synthesis of new dopamine might also be decreased due to the stimulation of greater numbers of presynaptic autoreceptors.These are just two studies conducted six to nine years ago involving only striatal tissue. They may not be at all relevant.
- Scott
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J Pharmacol Exp Ther 1993 Apr;265(1):103-11Monoamine oxidase-A inhibitors and dopamine metabolism in rat caudatus: evidence that an increased cytosolic level of dopamine displaces reversible monoamine oxidase-A inhibitors in vivo.
Colzi A, D'Agostini F, Cesura AM, Borroni E, Da Prada M
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.The effects of reversible inhibitors of monoamine oxidase-A (moclobemide, Ro 41-1049, both 20 mg/kg, i.p., and brofaromine, 10 mg/kg, i.p.) on the outflow of dopamine (DA) and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) as well as of 5-hydroxyindoleacetic acid was investigated by trans-striatal microdialysis in rats. These drugs markedly increased the level of DA in the dialysis fluid by 100% of basal values and concomitantly reduced the output of 3,4-dihydroxy-phenylacetic acid and homovanillic acid by 90%. The presence of tetrodotoxin in the perfusion fluid decreased the basal DA outflow and virtually abolished the rise in DA efflux after moclobemide administration. On the other hand, tetrodotoxin did not counteract the DA outflow induced by Ro 4-1284 (1 mg/kg, i.p.), a tetrabenazine derivative which rapidly releases DA from vesicles and causes a massive increase in the concentration of extravesicular amine. The injection of Ro 4-1284 30 min after moclobemide, brofaromine or Ro 41-1049 induced a 6-fold increase in DA outflow, which was accompanied by a transient increase in 3,4-dihydroxyphenylacetic acid levels. This latter effect was more marked for moclobemide than for the other two reversible inhibitors tested and was not observed in rats given the irreversible inhibitor clorgyline (5 mg/kg, i.p.). These results support the view that a large increase in the concentration of endogenous substrates in the cytosol might displace reversible monoamine oxidase-A inhibitors from the enzyme active sites. Therefore, the microdialysis technique seems to be a reliable in vivo method for assessing the degree of reversibility of monoamine oxidase inhibitors.
PMID: 8473998, UI: 93232983
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J Neural Transm Suppl 1990;32:79-84Effect of selective and reversible MAO inhibitors on dopamine outflow in rat striatum: a microdialysis study.
Colzi A, d'Agostini F, Kettler R, Borroni E, Da Prada M
Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.The effect of reversible inhibitors of the monoamine oxidase type A (MAO-A), moclobemide (Aurorix) and Ro 41-1049 (20 mg/kg i.p. each), as well as of reversible inhibitors of the MAO type B (MAO-B), Ro 19-6327 (1 mg/kg i.p.), on the outflow of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in the rat by transstriatal microdialysis. Reversible MAO-A inhibitors markedly increased the output of DA and concomitantly decreased the output of DOPAC and HVA. These effects were absent with the highly selective MAO-B inhibitor Ro 19-6327.
PMID: 2089114, UI: 91210769
poster:Scott L. Schofield
thread:15385
URL: http://www.dr-bob.org/babble/19991123/msgs/15781.html