Posted by Cam W. on November 17, 2001, at 11:51:48
In reply to new bupropion mode of action abstract- CAM,SLS,JG, posted by JohnX2 on November 17, 2001, at 9:36:17
John - It has ben widely known (ie. since Wellbutrin™ - bupropion - was relased) that the blockade of the reuptake of norepinephrine (NE) and dopamine (DA) could not be the mechanism of action of bupropion. The dose required to to effectively block the NE and DA reuptake mechanisms would have to be higher than 600mg/day. Since most people respond to dose of 300mg/day, scientists have been looking at the larger picture of bupropion mechansm of action.
Where and when was the study that you quoted published. I'd like to look over the article a little closer.
Also, reciprocal regulation of the locus ceruleus and raphe nuclei by serotonin (5-HT) and NE repspectively, has been also be known for a number of years. The same has been shown for the regulation of the VTA (ventral tegmental area - structure involving primary DA output).
Be careful interpreting your response to medications in terms of these circuits, though. Alterations in your undividual circuitry may account for some of the effects that you have noticed, but the body's conpensatory mechanisms (involving upregulation and downregulation of various neurotransmitter concentrations and their respective receptors and their receptor subtypes; involvement of endocrine, and other overlapping systems; changes in the gene expression of neuroactive enzymes and proteins, resulting from changes in second messenger signaling; etc.) , try to return the body to it's existing homeostatic state.
In simpler terms, there will be different short term and long term effects, potentially wide spread throughout the brain circuitry, in response to medications. While other serotonergic neurotransmission may not be affected increases in the concentration of NE, what other systems and brain structutres are affected by this increase in concentration? Then, how do these systems and structures affect the the components of the HPA axis (concentrations of CRH, ACTH, glucocorticoid receptors, cortisol levels), the interconnected and overlapping sex hormone system, etc.?
We have a lot of these pieces; now researchers should focus on putting it back together. I thank you for your insight into bupropion's mechanism of action and I think that you are on the right track to discovering where your personal "miswiring" is occuring, but don't forget the compensatory mechanisms, and the "collateral effects" in other brain areas and systems, resulting from increasing or decreasing any single neurotransmitter.
Thanks again for the insight. - Cam
poster:Cam W.
thread:84499
URL: http://www.dr-bob.org/babble/20011113/msgs/84506.html