Posted by Jill K. on March 3, 2002, at 22:33:50
In reply to Re: Wellbutrin increases or decreases dopamine?, posted by JohnX2 on March 3, 2002, at 18:04:20
Hello John,
Thanks for the info. Still some questions.
> Look, Wellbutrin is not the most well understood medicine in
> the world , but it is probably the MOST misquoted medicine in
> the world. Without looking at ANY of the clinical data on its
> mode of action, at SOLELY looking at behavioral tests of animal
> models and subsequent follow ups in human trials, there is every
> bit of evidence that Wellbutrin affects the dopamine system in
> responders to the medicine. In the animal models, when they look
> into the dopaminergic system, they often look for behaviours that
> are consistent with the administrations of dopaminergic medicines
> like amphetamines, which Wellbutrin passes the test.
> Also in human trials, Wellbutrin has been shown to be affective
> in disorders such as ADHD which are known to be dysruptions in the
> dopaminergic system. Also many responders to Wellbutrin report getting
> an amphetamine like feeling on the medicine.Desipramine is also very effective for ADHD, and it effects norepinephrine, not dopamine. Many people on desipramine also report an amphetamine like feeling. So I am not sure if this correlates with wellbutrin increasing dopamine.
> Now as far as clinical data. Many people base their opinions of the medicine
> on the parent compound bupropion hcl which has LITTLE IF ANY clinical value
> in the medicine what so ever. Wellbutrin (bupropion hcl) is what is known
> as a pro-drug, its metabolites (the thing the 1st pass of the liver breaks
> it down to, do almost all of the work). So looking strictly at binding assays, concentrations of, etc of bupropion
> hcl is of value, but gives a SERIOUS misconception of what is seriously going on. What has been discovered is that the active metabolites
> primarily hydroxy-bupropion and threohydroxybupropion accumulate at levels in
> the body so potent to make the dopamine reuptake properties substantial.
> It may be true that through some genomic mechanism the release of
> dopamine is diminished, possibly through a feedback mechanism. But this
> is even seen with norepineprine reuptake inhibitors, decreased firing,
> yet more noradrenaline in the synpatic cleft from the reuptake inhibition.
>
> Here is the best article I have read to date with
> a clear and concise summary of research findings
> on Wellbutrin (bupropion hcl) and myths/misconceptions
> regarding its dopaminergic mode of action:
>
> http://www.preskorn.com/columns/0001.html
>Dr Preskorn mentions that the metabolites of wellbutrin are much higher than the wellbutrin in the blood stream. He also shows a table that demonstrates that wellbutrin blocks dopamine and norepinephrine reuptake weakly. He then states that because the metabolites concentrations are so high, dopamine and norepinephrine reuptake inhibition occurs. He *did not* show the reuptake values for the metabolites though. Most metabolites, like desipramine (from imipramine) and norfluoxetine (from fluoxetine) are *norepinephrine* blockers, not dopamine.
> Best wishes,
> John
>Thanks. I hope to figure this out some day.
Jill
poster:Jill K.
thread:96141
URL: http://www.dr-bob.org/babble/20020301/msgs/96252.html