Pharmacol Biochem Behav. 1983 May;18(5):737-40.
Bupropion, d-amphetamine, and amitriptyline-induced conditioned taste aversion in rats: dose effects.

Miller DB, Miller LL.

Nine groups of rats (n = 6 per group) were adapted to a daily one-half hour period of water availability. When intake had stabilized, they were allowed access to a 0.1% (w/v) solution of saccharin, and immediately afterward were given IP injections of isotonic saline; bupropion HCl (10.0, 20.0, or 40.0 mg/kg); d-amphetamine-sulfate (0.5, 1.0, 2.0 mg/kg); or amitriptyline HCl (5.0, 10.0, or 20.0 mg/kg) in a volume of 1 ml. The lowest dose of each compound as chosen to be equipotent in screening tests used to identify potential antidepressants. Following 2 days of access to water alone, all groups were given a choice between water and saccharin for 3 consecutive days. All compounds induced taste aversions in a dose-related manner, but amitriptyline induced greater and longer-lasting aversions than either bupropion or d-amphetamine which were equipotent over the dose range studied. As such, this is the first demonstration that bupropion and amitriptyline, two clinically effective antidepressants, can induce taste aversions and replicates as well the common finding that d-amphetamine has substantial taste aversion-inducing properties. The ability of these compounds to induce taste aversions could be mediated through their effects on central catecholaminergic processes although amitriptyline has significant peripheral anticholinergic effects.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6407035&dopt=Abstract Bupropion Wellbutrin




Eur J Clin Pharmacol. 1984;27(1):75-80.
The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man.

Hamilton MJ, Bush MS, Peck AW.

The effects of bupropion and ethanol were examined alone and in combination in a placebo controlled, double-blind, crossover study in 12 healthy volunteers. Results were subjected to analysis of variance and differences of p less than 0.05 taken as significant. In the main study using the Wilkinson auditory vigilance test, no active treatment or combination of treatments produced significant change compared with placebo. However, when compared with bupropion 100 mg, vigilance was significantly impaired by 32 ml alcohol alone though not when combined with bupropion. No significant changes in reaction time or short term memory occurred. Visual analogue scales indicated that the subjects were mentally slower after alcohol 32 ml than after placebo. Combination of bupropion 100 mg with alcohol 32 ml abolished this difference. A similar pattern occurred with group ratings indicating mental sedation. Subjects were clearly able to differentiate between the 16 ml and 32 ml doses of alcohol when assessing their degree of inebriation. Combination of bupropion with alcohol made no difference to the ratings of inebriation. The top dose of alcohol tended to increase energy in the low frequency EEG bands. Combination of the top alcohol dose with bupropion, however, produced a significant reversal with lowered energy in the 4-7.5 Hz band. Combination of bupropion with alcohol failed to change the blood alcohol concentration achieved.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6436033&dopt=Abstract Bupropion Wellbutrin




J Pharm Sci. 1984 Aug;73(8):1104-7.
Determination of bupropion and its major basic metabolites in plasma by liquid chromatography with dual-wavelength ultraviolet detection.

Cooper TB, Suckow RF, Glassman A.

A method for the determination of bupropion and its three major basic metabolites in plasma is described. Following an extraction from alkaline plasma into 1.5% v/v isoamyl alcohol in n-heptane, a portion of the acid-backwashed extract was injected onto a column packed with trimethylsilyl reverse-phase material and eluted with a phosphate buffer-acetonitrile (80:20) mobile phase containing an ion-pairing reagent and triethylamine. The compounds were detected with a dual-wavelength UV detector (214 and 254 nm) to optimize sensitivity and facilitate simultaneous detection. The method provides an absolute recovery of approximately 85% for bupropion and approximately 98% for the metabolites. Day-to-day reproducibility did not exceed 4.0% for all compounds. The detection limits were approximately 5 ng/mL for bupropion and 100 ng/mL for the major metabolites. The limit of 100 ng/mL for metabolite quantitation is imposed by the internal standard concentration selected for steady-state studies. In single-dose pharmacokinetic studies, 10% of the steady-state concentration of internal standard was used; this permitted a 10-ng/mL lower limit of detection. Steady-state plasma levels of bupropion and the metabolites from eight different patients are presented.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6436464&dopt=Abstract Bupropion Wellbutrin




Psychopharmacology (Berl). 1980 Feb;67(2):111-8.
Stimulus properties of antidepressants in the rat.

Jones CN, Howard JL, McBennett ST.

Various doses of bupropion HCl (Wellbatrin) (5, 10, and 20 mg/kg), a new phenylaminoketone antidepressant, were employed as cues in a two-lever operant discrimination from saline control injections in rats on an FR10 schedule of food reinforcement. Subjects reached and maintained a high level of discrimination in the O vs 20 mg/kg bupropion stimulus condition but not at the lower doses. In generalization testing, the following compounds produced dose-related responding on the bupropion lever: viloxazine, nomifensine, caffeine, d-amphetamine, cocaine, methylphenidate, and benzylpiperazine. Drugs that failed to show dose-related generalization included phenethylamine, thyrotropin-releasing hormone, imipramine, nortriptyline, amitriptyline, desipramine, mianserin, chlordiazepoxide, diazepam, scopolamine, phenobarbital, and morphine. With the important exception of viloxazine, the generalization profile of bupropion seems to reflect its previously reported locomotor stimulant effects in the rat rather than its antidepressant activity and suggests that species differences exist between man and rat with regard to the pharmacologic activity of this new antidepressant.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6768086&dopt=Abstract Bupropion Wellbutrin




J Pharmacol Exp Ther. 1980 Oct;215(1):127-34.
Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo.

Cooper BR, Hester TJ, Maxwell RA.

Bupropion (BW 323U; Wellbutrin), a novel compound with antidepressant effects in man, was found to reduce immobility in an "experimental helplessness" forced swimming antidepressant test in rats as did imipramine and amitriptyline. Higher doses produced elevated locomotor activity in an automated open field and produced stereotyped sniffing which was contrasted with apomorphine. When bupropion or desmethylimipramine was given before intracisternal injections of 6-hydroxydopamine, bupropion produced a dose-related selective antagonism of the destruction of dopamine neurons, while under the same conditions, desmethylimipramine produced a dose-related selective antagonism of the destruction of noradrenergic neurons. Studies in which the dose of bupropion and the dose of 6-hydroxydopamine were varied revealed that a dose-related selective antagonism of dopamine depletion by 6-hydroxydopamine occurred when doses up to and including 50 mg/kg i.p. to bupropion were administered. Some antagonism of norepinephrine depletion also occurred at 100 mg/kg of bupropion i.p. Bupropion also selectively reversed the dopamine depletion produced by alpha-methyl-m-tyrosine, a finding which is consistent with the view that bupropion is a dopamine uptake inhibitor in vivo. The importance of dopamine systems for the behavioral effects of bupropion were also studied. When the locomotor stimulant effects of bupropion were tested in rats with chronic destruction of dopamine neurons produced by 6-hydroxydopamine, bupropion failed to elevate locomotor activity. Rats treated with procedures using 6-hydroxydopamine to produce relatively selective norepinephrine depletions responded to bupropion with locomotor activity stimulation like controls. Rats with similar depletions of either dopamine or norepinephri