Posted by bodhisattva_guy on February 6, 2011, at 4:14:19
In reply to Re: Wellbutrin milder than Adderall? » SheilaC, posted by Chairman_MAO on February 3, 2011, at 14:52:44
Bupropion cannot be milder or stronger than adderall because these two medications work on different receptors. Furthermore, bupropion can become as stimulating as adderall if the dose is large enough. I've experienced psychosis-like paranoia while on bupropion. This can also happen on adderall, so it is hard to say which is milder. They belong to different group of medications.
[doc] type
http://www.unc.edu/~novick/bupropion.docexcerpt from:
"Chemically Correct: Bupropion
By
Andrew Novick"Hopes this helps:
wellbutrin chemical formula: http://upload.wikimedia.org/wikipedia/commons/0/03/Bupropion_numbered.png
dextroamphetamine: http://cerhr.niehs.nih.gov/evals/stimulants/amphetamines/amphetamine.gifDopamine
Bupropion has relatively weak yet selective affinity for the dopamine re-uptake pump (4). Its much weaker than cocaine as an inhibitor of dopamine re-uptake (5), and even sertraline (which is considered a Selective Serotonin Re-uptake Inhibitor) has a stronger in vitro affinity for the dopamine transporter (4). Yet, despite bupropions lack of potency, meaningful dopaminergic activity appears to take place, as bupropion can effectively substitute in rats for a plethora of dopaminergic stimulants from cocaine to methamphetamine (6,7). In vivo, bupropion increases interstitial dopamine concentrations (8), can prevent dopamine depletion from the neurotoxic effects of 6-hydroxydopamine (9,10), and increases dopamine transporter mRNA expression (11).
Bupropions dopamine controversy comes into focus when we see that when given to humans at actual clinical dosages, bupropion fails to significantly occupy the dopamine transporter compared to placebo (12). Also, unlike other dopaminergic drugs, bupropion doesnt affect prolactin and growth-hormone levels in humans at clinical dosages (13). Furthermore, if bupropion did have pronounced dopaminergic and stimulant qualities, it might be expected to appeal to stimulant abusers. However, at therapeutic dosages, experienced stimulant users have a hard time distinguishing bupropion from placebo (14). Yet at dosages slightly above the usual therapeutic level, bupropion does produce mild amphetamine and liking effects in test subjects (15).
Probably the best conclusion that can be drawn from this conflicting research is that because of bupropions weak affinity for the dopamine re-uptake pump, pronounced dopaminergic activity doesnt kick in until the higher dosages.
Noradrenaline
Bupropions affinity for the noradrenaline re-uptake pump is approximately half that of its affinity for the dopamine pump (16). Despite being less potent at inhibiting noradrenaline re-uptake, most of bupropions antidepressant action is attributed to its noradrenergic mechanisms (17). How can this be? Bupropions active metabolite, hydroxybupropion has almost equal affinity for the NA re-uptake pump as bupropion yet its concentrations during clinical treatment reach 6-fold that of the parent drug (17). This increase in concentration would make up for the lack of affinity and thus cause meaningful inhibition of NA re-uptake, even at therapeutic dosages. Hydroxybupropion has been said to be more antidepressant and less stimulant due its noradrengeric mechanism with lack of dopaminergic action (18). But well talk more about hydroxybupropion and other metabolites later.
Bupropion downregulates beta-adrenergic receptors (a trademark of most antidepressants with NA activity) and decreases NA stimulation of adenylate cyclase (19). It also reduces the firing rate of NA neurons, a phenomenon which can be reversed by the administration of adrenergic antagonists (16,20). There is also evidence that bupropion increases the release of NA from the synapse (20).
Serotonin
Traditionally, bupropion was thought to have no action on serotonin, being that its affinity for the serotonin re-uptake pump is negligible (21). However, a more recent study has demonstrated that bupropion increased the firing rate of serotonergic neurons, possibly by an NA facilitated mechanism (20).
Also of interest might be the synergistic role that serotonin itself can play with other neurotransmitters and how this could apply to bupropion. Fluoxetine (better known as Prozac, a serotonin re-uptake inhibitor) can greatly potentiate bupropions extracellular increases of dopamine and serotonin (22). There is some evidence that fluoxetine itself can be used for weight loss (23), and a bupropion-fluoxetine combination would resemble the once popular noradrenergic-serotonergic combination Phen-fen.
Nicotinic
Bupropions efficacy as an anti-smoking aid can be attributed to two reasons: 1) bupropion acts as a nicotine substitute (24,25) and 2) bupropion acts as a nicotinic antagonist (26). Besides sharing similar stimulant properties with nicotine, bupropion has modest selectivity for neuronal nicotinic receptors, particularly blocking activation of alpha(3)beta(2), alpha(4)beta(2) and alpha(7) neuronal acetylcholine nicotinic receptors, thus blunting the effects of nicotine. (26)
Pharmacokinetics (15)
When administered orally, peak concentrations of bupropion occur within 1-3 hours and 84% of it is bound to plasma protein. The half-life of bupropion is anywhere from 10-21 hours. It is metabolized in the liver to form three active metabolites: hydroxybupropion, threohydrobupropion and erythrohydrobupropion. Hydroxybupropion is the most potent of the metabolites and has a half-life of 20-25 hours. As stated earlier, hydroxybupropion concentrations reach several times that of the parent drug. Elimination occurs mainly through the urine.
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URL: http://www.dr-bob.org/babble/20110130/msgs/978747.html