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Re: How does Wellbutrin work ? SLS

Posted by JohnX on March 9, 2001, at 2:33:56

In reply to Re: How does Wellbutrin work ? JohnX, posted by SLS on March 2, 2001, at 8:58:31

> > I read an article which debated the mechanism of action of Wellbutrin based off of experimental data. The conclusion was that the metabolite hydroxy-bupropion (as Stahl indicates) does most of the work via norepinephrine re-uptake. In the animal models at therapeutic doses, the dopamine reuptake was insignificant. However, they did hypothesize that an unknown genomic mechanism was responsible for increasing the sensitivity of dopamine receptors in the nucleus accumbens.
> Dear JohnX,
> Thank you. This seems very reasonable.
> The involvement of NEergic activity has been suspected by many for a long time, but the mechanism remained elusive. Who would have thought to be smart enough to test active metabolites? ;-)
> The nucleus accumbens think is very exciting.
> > How well the animal models correlate to people
> > is a good topic of debate.
> It depends on the glue.
> (Stupid, I know, but I smiled, and that's all that counts).
> :-)
> - Scott

some other notes:

A lot of the action occured in the locus coereleus
(spelled right?) part of the brain where NE turnover was slowed down substantially.

Their was a decrease in tryrosine-hydroxylase immunreactivity (the limiting step in dopamine and NE production).
Down-regulation of beta-adrenoreceptors was not
noted at therapeutic doses.

I'm guessing that the genomic decrease in tyrosine-hydroxylase sensitizes the dopamine post receptors since the dopamine reuptake is minimal to counteract this. But the norepinephrine reuptake probably counteracts the effect in the norepinephrine neurons which would explain the lack of beta-adrenoreceptor down-regulation.

I still think there is some splainin to do!





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