Psychopharmacology (Berl). 2001 Apr;155(1):52-7.
Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment.

Dong J, Blier P.

Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100256, Gainesville, FL 32610, USA.

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




Neuropsychopharmacology. 1992 Aug;7(1):7-14.
Effects of chronic bupropion on interstitial concentrations of dopamine in rat nucleus accumbens and striatum.

Nomikos GG, Damsma G, Wenkstern D, Fibiger HC.

Department of Psychiatry, University of British Columbia, Vancouver, Canada.

Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake. The present experiments investigated the effects of acute (10 mg/kg, twice daily for 2 days) and chronic (10 mg/kg, twice daily for 21 days) bupropion treatment on interstitial DA concentrations using simultaneous in vivo microdialysis in the nucleus accumbens (NAC) and striatum of awake freely moving rats. Compared to animals that had not previously been exposed to the drug, bupropion (25 mg/kg, IP) induced increases in extracellular DA were significantly enhanced in the NAC of the chronic but not the acute bupropion group. This effect was regionally selective, as it was not observed in the striatum. In accordance with previous reports, concurrent behavioral measurements indicated that the locomotor stimulant effects of bupropion were also enhanced in the chronic group. These results demonstrate that bupropion-induced behavioral sensitization is accompanied by a selective potentiation of the effects of this compound on interstitial DA concentrations in the NAC.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1381923&dopt=Abstract Bupropion Wellbutrin




Biol Psychiatry. 1992 Nov 1;32(9):834-8.
Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome.

Goodnick PJ, Sandoval R, Brickman A, Klimas NG.

Department of Psychiatry, University of Miami, Florida 33136.

Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion. In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01). Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1450297&dopt=Abstract Bupropion Wellbutrin




J Anal Toxicol. 1995 Mar-Apr;19(2):69-72.
A high-performance liquid chromatographic method for quantitating bupropion in human plasma or serum.

Jennison TA, Brown P, Crossett J, Urry FM.

Associated Regional and University Pathologists, Inc., Salt Lake City, UT 84108, USA.

We report a high-performance liquid chromatographic (HPLC) procedure for quantitating bupropion in serum or plasma for the purpose of therapeutic monitoring. Bupropion and its internal standard, a fluorinated analogue of bupropion, are extracted into hexane-isoamyl alcohol (96:4) after the addition of 400 microL 0.1N KOH. The organic phase is evaporated, reconstituted with 200 microL acetonitrile, and then analyzed on a silica column using a mobile phase consisting of 95% methanol and 5% NH4H2PO4. The ultraviolet detector is set to monitor 248 nm. Within-run and total precision at a therapeutic concentration of 30 ng/mL are 5.2 and 8.5%, respectively. The lower limit of quantitation is 5 ng/mL, and the upper limit of linearity is 400 ng/mL. More than two dozen drugs and metabolites were tested for interference; fluoxetine was the only analyte demonstrating a retention time that would interfere with bupropion quantitation. Chromatographic analysis time per injection is less than 7 min. This procedure combines a single-step extraction with HPLC analysis to provide rapid and reliable analysis of bupropion.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7769789&dopt=Abstract Bupropion Wellbutrin




J Clin Psychiatry. 1995 Jun;56(6):260-4.
Prescribing trends of antidepressants in bipolar depression.

Zarate CA Jr, Tohen M, Baraibar G, Kando JC, Mirin J.

Pharmacoepidemiology Center, McLean Hospital, Belmont, Mass. 02178, USA.

BACKGROUND: This study utilizing pharmacoepidemiologic methods was undertaken to determine the prescribing patterns of antidepressants particularly in bipolar depression. METHOD: From pharmacy records of the McLean Hospital, the number of patients receiving antidepressants and given electroconvulsive therapy (ECT) from June 1, 1987, to May 8, 1993, was determined. We later linked these data bases with patients who were diagnosed with DSM-III-R bipolar depression (296.5) during the same period of time. RESULTS: During the 6-year period, it was determined that 3829 inpatients had received tricyclic antidepressants (TCAs), 2981 fluoxetine, 2603 trazodone, 809 bupropion, 743 monoamine oxidase inhibitors (MAOIs), 592 stimulants, 588 sertraline, 48 paroxetine, and 894 ECT. There were significant increases over time in prescriptions of MAOIs compared with fluoxetine (chi 2 = 14.36, p = .006), and bupropion compared with TCAs (chi 2 = 6.45, p = .04). There was a trend for bupropion to be prescribed more over time compared with fluoxetine (chi 2 = 5.09, p = .08). There were no significant changes in the prescribing of other antidepressants or in the use of ECT. CONCLUSION: At our center, prescribing of bupropion and MAOIs in bipolar depression has increased significantly. This may be related to the reports in the literature of the low switch rates to mania with the use of these drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7775368&dopt=Abstract Bupropion Wellbutrin