Posted by JohnX on March 2, 2001, at 3:50:03
In reply to Re: How does Wellbutrin work ? » SLS, posted by Sunnely on February 23, 2001, at 22:07:02
> Stephen M. Stahl, MD (Essential Psychopharmacology, 2000, 2nd ed., Cambridge University Press, Cambridge, UK) explains it this way:
>
> "Bupropion is the prototypical agent of the norepinephrine and dopamine reuptake inhibitors. For many years, its mechanism of action was unclear. Bupropion itself has weak reuptake properties for dopamine, and weaker yet reuptake properties for norepinephrine. The action of the drug on norepinephrine and dopamine neurotransmission, however, has always appeared to be more powerful than these properties could explain, which has led to proposals that bupropion acts rather vaguely as an adrenergic modulator of some type. Bupropion is metabolized to an active metabolite, which is not only a more powerful norepinephrine reuptake blocker than bupropion itself but is also concentrated in the brain. In some ways, therefore, bupropion is more of a pro-drug (i.e., precursor) than a drug itself. That is, it gives rise to the "real" drug, namely its hydroxylated active metabolite (hydroxybupropion), and it is this metabolite that is the actual mediator of antidepressant efficacy via norepinephrine and dopamine reuptake blockade."
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> ===============================================
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> > How does Wellbutrin (bupropion) work?
> >
> >
> > - ScottScott,
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.
How well the animal models correlate to people
is a good topic of debate.-JohnX
poster:JohnX
thread:54696
URL: http://www.dr-bob.org/babble/20010221/msgs/55305.html