J Pharm Pharmacol. 1984 Mar;36(3):208-10.
Effect of bupropion on dopamine and 5-hydroxytryptamine-mediated behaviour in mice.

Muley MP, Joshi MA, Manekar MS.

When bupropion (12.5-50 mg kg-1) was administered 30 min before methamphetamine it significantly antagonized methamphetamine-induced stereotyped behaviour in mice, but when given 5 min after methamphetamine it significantly potentiated the behaviour. When it was administered to mice pretreated with 100 mg kg-1 pargyline, intense locomotor stimulation and stereotyped behaviour was observed whereas when clomipramine was administered similarly the animals showed locomotor stimulation, head twitches and abduction and extension of hind limbs. Unlike clomipramine, bupropion failed to potentiate the 5-hydroxytryptamine-mediated behaviour seen after 5-hydroxytryptophan, 100 mg kg-1, i.v. These observations are in agreement with reports that bupropion is more potent as an inhibitor of dopamine uptake than as an inhibitor of 5-hydroxytryptamine uptake in-vitro.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6144762&dopt=Abstract Bupropion Wellbutrin




Adv Biochem Psychopharmacol. 1982;31:277-86.
Neurochemical and neuropharmacological investigations into the mechanisms of action of bupropion . HCl--a new atypical antidepressant agent.

Ferris RM, Maxwell RA, Cooper BR, Soroko FE.

In the present study, bupropion has been shown to be effective in several behavioral models predictive of antidepressant activity suggesting that it should be an effective antidepressant in man. Furthermore, the data also show that the antidepressant activity of the drug cannot be due to its ability to inhibit MAO present in brain or to increase the release of biogenic amines from nerve endings. It also appears unlikely that the weak properties of the drug as an inhibitor of catecholaminergic pumps in brain csn explain its antidepressant activity. However, the weak but selective block of dopaminergic pumps observed in vivo can be correlated with the mild CNS stimulant properties observed in rodents. Bupropion, failed to desensitize beta-adrenergic receptors in rat cerebral cortex in chronic studies and exhibited equivocal results in acute studies. These neurochemical properties of bupropion serve to distinguish it from typical antidepressants of the MAOI and tricyclic classes and suggest that it should be classified as an atypical antidepressant, whose mechanism of action must still be elucidated.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6282058&dopt=Abstract Bupropion Wellbutrin




Neuropharmacology. 1983 Jul;22(7):927-9.
Daily bupropion injections for 3 weeks attenuate the NE stimulation of adenylate cyclase and the number of beta-adrenergic recognition sites in rat frontal cortex.

Gandolfi O, Barbaccia ML, Chuang DM, Costa E.

In rats receiving daily doses (50 mg/kg i.p. twice daily) of bupropion HCI (WellbutrinR) repeated for 21 days the Bmax of the beta-adrenergic receptor recognition sites located in the frontal cortex is reduced. This decrease is not associated with a decrease of the apparent affinity of these recognition sites. However the Vmax of the cAMP (cyclic AMP) generating system stimulated by NE is reduced suggesting that similarly to other antidepressants bupropion down regulates beta-adrenergic receptors located in the frontal cortex. Bupropion neither inhibits MAO (monoamine oxidase) nor releases biogenic amines but only weakly inhibits monoamine uptake in vitro.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6312356&dopt=Abstract Bupropion Wellbutrin




Neuropharmacology. 1983 Nov;22(11):1257-67.
Bupropion: a new antidepressant drug, the mechanism of action of which is not associated with down-regulation of postsynaptic beta-adrenergic, serotonergic (5-HT2), alpha 2-adrenergic, imipramine and dopaminergic receptors in brain.

Ferris RM, Beaman OJ.

The present experiments were undertaken to determine: (1) whether bupropion had any direct effects on receptors present in rat brain; (2) whether the drug could down-regulate postsynaptic beta-adrenergic, alpha 2-adrenergic, serotonergic, imipramine and dopaminergic receptors after chronic administration, as had been demonstrated for tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, electroconvulsive therapy (ECT) and "atypical" antidepressants. Bupropion was found to be weak or inactive when its affinity for 14 different receptors present in brain was assessed by binding assays. The drug failed to desensitize beta-adrenergic receptors in the cerebral cortex of the rat as determined by [3H]dihydroalprenolol binding, after being administered at 25 mg/kg (i.p.) once a day for 6 weeks, or after being administered by the intraperitoneal route to rats at doses as large as 150 mg/kg per day for 4 days. When administered at doses of 37.5, 75 and 150 mg/kg per day for 21 days, the drug had no effect on beta-adrenergic, alpha 2-adrenergic, imipramine or serotonergic (5-HT2) receptors in the brain of the rat as determined by Scatchard analysis of the binding data. These data show that the antidepressant activity of bupropion is not associated with a down-regulation of receptors in the CNS commonly implicated in the mechanism of action of antidepressant drugs. Bupropion also produced a dose-dependent tendency to decrease the activity of norepinephrine-stimulated adenylate cyclase in slices of cerebral cortex obtained from rats treated chronically with the drug. However, the decrease was highly variable, was most obvious in tissues obtained from rats receiving large, non-pharmacologically relevant




Clin Chem. 1983 Mar;29(3):462-5.
Radioimmunoassay for bupropion in human plasma: comparison of tritiated and iodinated radioligands.

Butz RF, Smith PG, Schroeder DH, Findlay JW.

We evaluated the potential usefulness of 125I-labeled p-hydroxybupropion in a direct radioimmunoassay for bupropion in human plasma as compared with a currently used [3H]bupropion dextran-coated charcoal method. In both radioimmunoassay methods succinoylpropylbupropion antiserum was used that was highly specific for unchanged drug, cross reactivities with known bupropion metabolites being less than 0.3%. However, the use of 125I-labeled p-hydroxybupropion afforded greater sensitivity (0.3 microgram/L vs 0.6 microgram/L with [3H]bupropion) and was readily adaptable to the more convenient polyethylene glycol separation method. Between-assay CVs were 3.8 to 12.2% (mean 7.6%) with the 125I-based radioimmunoassay and 5.1 to 11.5% (mean 7.5%) with the 3H-based assay. Agreement between the two radioimmunoassay determinations of buproprion in human plasma samples collected over a 60-h period after oral drug administration was excellent (slope = 1.086, r = 0.989). We find the 125I-based assay a convenient and suitable alternative to the [3H]bupropion assay in pharmacokinetic studies in humans.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6402324&dopt=Abstract Bupropion Wellbutrin