Posted by JohnX2 on March 26, 2002, at 18:02:09
In reply to Re: Wellbutrin and Serotonin, posted by JohnX2 on March 26, 2002, at 17:09:56
BTW, if Wellbutrin indeed had a potent cross diffusion of noradrenaline to alpha-1 receptors perhaps this would give it a "built in" Provigil effect (an alpha-1 agonist) on top of the rest of its actions.Yes/No?
John
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> djmm, thanks for the informative post!
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> Here was Dr. Blairs absract on Wellbutrin that I found interesting. I saw this a while back. I wondered if Wellbutrin may increase sertonergic firing via an indirect noradrenergic path based off responses I got (alpha-1 stimulation of somatodendric serotonin receptors), and he does too. I think this effect may be dose dependant (I think the serotonergic action is at a very high dose, maybe above therapeutic). More Wellbutrin mystery.....
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11374336&dopt=Abstract
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> 1: Psychopharmacology (Berl) 2001 Apr;155(1):52-7 Related Articles, Books, LinkOut
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> Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment.
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> Dong J, Blier P.
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> Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100256, Gainesville, FL 32610, USA.
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> RATIONALE: Bupropion is widely used in the treatment of depression and as an anti-craving medication for the cessation of tobacco smoking. Because it is a very weak inhibitor of norepinephrine (NE) and dopamine (DA) reuptake, its mechanisms of action remain to be elucidated. METHODS: Bupropion was administered subcutaneously via osmotic minipumps over 2 days to determine its effects on the spontaneous firing activity of NE, serotonin (5-HT), and DA neurons in the brain of anaesthetised male Sprague-Dawley rats. This treatment was used in order to obtain levels of the parent compound and its putatively active metabolites that would more adequately reflect the clinical condition than utilizing acute injections. RESULTS: When given by minipump for 2 days, bupropion produced a dose-dependent attenuation of the mean spontaneous firing NE neurons (7.5 mg/kg per day: 15%; 15 mg/kg per day: 61%; 30 mg/kg per day: 80%) which was reversed by the alpha 2-adrenoceptor antagonist idazoxan. At the highest regimen, the mean firing rate of 5-HT neurons was 100% higher than in control rats, but unaffected in NE-lesioned rats. In contrast, DA neurons in the ventral tegmental area displayed a normal firing rate during the latter bupropion treatment. CONCLUSIONS: Sustained bupropion administration decreased the firing rate of NE neurons due to an increased activation of their inhibitory somatodendritic alpha 2-adrenoceptors. This effect of the bupropion treatment would be attributable mainly to an enhancement of NE release and not to reuptake inhibition. This contention is based essentially on the observation that NE reuptake blockers leave unaltered the firing rate of 5-HT neurons, whereas bupropion enhanced it via a NE-dependent mechanism. The present study did not put into evidence any DA activity of bupropion at the level of the cell body of mesolimbic/cortical DA neurons at a regimen exerting profound alterations of the firing activity of NE and 5-HT neurons.
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> PMID: 11374336 [PubMed - indexed for MEDLINE]
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