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Re: ok, here is the cyp2d6 dopamine hypothesis

Posted by Anna Laura on June 22, 2002, at 7:44:59

In reply to ok, here is the cyp2d6 dopamine hypothesis, posted by JohnX2 on June 21, 2002, at 0:58:12


> >
> > Wellbutrin has a very narrow therapeutic range.
> > It is actually a pro-drug (the parent compound
> > bupropion is not involved much in the response, it
> > is the metabolites, pricipally hydroxybupropion that
> > are believed to do the work). The metabolites have
> > a longer 1/2 life (like 20+ hrs for hydroxybupropion),
> > and so they take a while to build up in your body and
> > reach a steady state. Just a guess, but its possible you
> > "passed through" the therapeutic window, maybe lowering the
> > dosage would help.
> >
> > Some people believe that wellbutrin at really strong doses
> > (metabolites above the thereapeutic range), actually indirectly
> > increases the firing of serotonin neurons via an interaction
> > between the increased Noradrenaline and serotonin.
> >
> > This is another off the wall hypothesis....
> >
> > One of the metabolites hydroxybupropion is believe to
> > primarily be metabolized through the liver enzyme CYP 2D6.
> > At very high levels I believe it may swamp that enzyme.
> > I read a paper once suggesting that medicines that inhibit
> > CYP 2D6 may cause EPS. I don't remember the working hypothesis
> > though and it wasn't really substantiated (more of a guess).
> > I should try to dig that one up.
> >
> > Just some wild guesses.
> >
> > Good Luck,
> > John
>
>
> This is from
> "CYP 2d6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects"
> Medical Hypothesis (1996) 47, 439-442
> P. Vandel, B. Bonin, S. Vandel, D. Scheter, P. Bizouard
>
>
> Quick and dirty summary:
> - "The cyp 2d6 isoenzyme has been detected in the brain"
> - "From animal data, there is evidence that cyp 26d is
> involved in the metabolism of dopamine in the brain."
> - "There is a genetically determined deficiency in cyp 2d6
> and Parkinson's disease"
> - examples of non psychiatric meds that inhibit 2d6 and
> may induce dopamine related psychiatric illness. One med is
> quinidine (a heart med).
>
> So there it is.
>
> I would also like to note that about 1 in 20 caucasions
> is a poor metabolizer of cyp 450 2d6. This means a drug
> that needs it for a substrate can easily become toxic.
> *Many* psychotropic meds use this enzyme of inhibit it.
>
> Curiously, few resistant patients are tested for poor
> cyp 450 2d6 metabolism.
>
> John


Thanks for answering John,


I think i'm going to get screened for cyp 450 2d6 metabolism.
I have to take a SPECT with a dopaminergic "tracking" sometime soon; i'm going to have 2d6 checked too, i have nothing to loose anyway.
As far as Wellbutrin dosing is concerned i wouldn't hazard messing up with that .
I guess i'm going to wait a little longer (i'm on the third day of 450 mg. dose). Strangely, i feel kind of "sleepy": i get a weird mellow feeling; is far from being a "feeling good" sensation, but it's not bad either. It's somehow neutral, much like a benzo.
I recently called the Neuroscience University Clinic i've been at a couple of months ago; I went down there in mid April; after a few days of screening and interviewing they came up with a bipolar II dx, and suggested me to take a mood-stabilizer. When i called them back a couple of days ago they wondered why i haven't been prescribed for a mood stabilizer as they have been suggested;

When i flied back home two months ago (the center is down South) i went to a local pdoc to get a prescription for Neurontin, but he wouldn't prescribe me that, stating that even though i had been hyperthymic for many years (had a "hypomanic phase" lasting a few months before crashing down and sinking in to depression ) i didn't run any serious risk of getting manic ; moreover, -he argued- i was apathetic/anhedonic,unmotivated and kind of slowed down, so i didn't need a mood stabilizer that was possibly going to put me down even further and sedate me;
Who's right? I don't know that yet. What would you suggest?


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poster:Anna Laura thread:110261
URL: http://www.dr-bob.org/babble/20020617/msgs/110468.html