Posted by MB on February 13, 2004, at 12:59:52
I remember not to long ago when Wellbutrin was discussed as a dopamine drug...mainly increasing dopamine levels. Does anybody remember this? It was tried out on cocaine addicts to increase dopamine levels and reduce their cravings for cocaine. Now all the literature refers to it as a norepinephrine drug. I've even read that dopamine isn't affected until doses are given that exceed what any human would take. But *then*, in the same literature, it is postulated that bupropion helps smokers by increasing dopamine levels. Here's what I found. What gives?
MB_______________________________
"Nervous System Effects
The precise mechanism of antidepressant action of bupropion is unclear, although noradrenergic pathways appear to be principally involved. Bupropion doses that were active in animal models of depression selectively inhibit firing of noradrenergic neurons in the locus ceruleus in animals;hydroxybupropion, an active metabolite, produces similar inhibition. In patients with depression receiving bupropion, whole-body turnover of norepinephrine is reduced, which also has been observed with various other therapies for depression.However, the reduction in whole-body turnover of this neurotransmitter observed with bupropion may not be related principally to inhibition of norepinephrine uptake,and the drug is substantially less potent than tricyclic antidepressants (e.g., amitriptyline, imipramine) in inhibiting such uptake.In addition, unlike tricyclic antidepressants, bupropion appears to have little effect on the reuptake of norepinephrine or serotonin at the presynaptic neuronal membrane.Although reuptake of dopamine is inhibited to some extent and more extensively than by these tricyclic antidepressants, such inhibition with bupropion occurs at dosages higher than those required for antidepressant activity.Circulating concentrations of prolactin or growth hormone are not altered by bupropion or its metabolites,and neither type A nor B monoamine oxidase (MAO-A, MAO-B) is inhibited by the drug.In addition, bupropion does not exhibit clinically important anticholinergic, antihistaminic, or α-adrenergic blocking activity.Unlike most other antidepressants, bupropion also does not appear to suppress rapid eye movement (REM) sleep.The precise mechanism of action responsible for the efficacy of bupropion as an adjunct in the cessation of smoking is unclear, although noradrenergic and/or dopaminergic effects presumably are involved.It has been suggested that CNS effects of dopamine might be involved in the reinforcement properties of addictive drugs and that nicotine withdrawal manifestations may involve the absence of CNS effects of norepinephrine that are mediated by nicotine.Efficacy of bupropion in smoking cessation does not appear to depend on the presence of underlying depression.Dose-related CNS stimulation occurs with bupropion in animals, which exhibit increases in locomotor activity and in the rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior. Seizures occur in animals at doses approximately tenfold greater than the usual antidepressant dose in humans."
poster:MB
thread:312868
URL: http://www.dr-bob.org/babble/20040210/msgs/312868.html