Eur Neuropsychopharmacol. 1996 Nov;6(4):299-303.
Bupropion induces sniffing: a possible dopaminergic mechanism.

Zarrindast MR, Hodjati MR, Pejhan A, Soleimannejad E.

Department of Pharmacology, School of Medicine, University of Tehran, Iran.

The effect of bupropion, an antidepressant drug, on sniffing behaviour was examined in rats. Animals treated intraperitoneally (i.p.) with different doses of bupropion (5-40 mg/kg) showed sniffing behaviour in a dose-related manner. Pretreatment of animals (i.p.) with the dopamine antagonists SCH 23390 (0.025-0.1 mg/kg) or sulpiride (12.5-50 mg/kg) decreased the sniffing induced by bupropion. Reserpine pretreatment (2.5 mg/kg, i.p., 18 h) alone and in combination with alpha-methyl-p-tyrosine (AMPT; 250 mg/kg, i.p.) also reduced the behaviour produced by the drug. The alpha-adrenoceptor phenoxybenzamine (5 and 10 mg/kg, i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg, i.p.) administered 60 min prior to bupropion did not affect the drug's effect on sniffing. Propranolol alone, however, induced sniffing. The antimuscarinic atropine (5 and 10 mg/kg, i.p.) administered 30 min prior to bupropion increased the bupropion response. Atropine alone induced vigorous sniffing. It is concluded that bupropion induced sniffing through a dopaminergic mechanism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8985713&dopt=Abstract Bupropion Wellbutrin




J Pharmacol Exp Ther. 1997 Apr;281(1):508-13.
Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine.

Tella SR, Ladenheim B, Cadet JL.

Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007-2195, USA.

Inhibition of dopamine (DA) transporter function is thought to be the principal mechanism underlying cocaine's addictive effects. In contrast to cocaine, several other inhibitors of DA transporter function are not considered to possess abuse liability. One of the neuroadaptive changes to chronic cocaine self-administration is the up-regulation of DA transporters. In the present study, we investigated the reinforcing and neuroadaptive effects of two other DA reuptake inhibitors, namely bupropion and nomifensine. Drug-naive rats readily acquired and subsequently maintained consistent self-administration of 3 and 1 mg/kg/infusion doses of bupropion and nomifensine, respectively, during 2-hr daily sessions over a prolonged period. Similarly, self-administration responding at low doses of bupropion (0.75 and 1.5 mg/kg/infusion) and nomifensine (0.1 and 0.3 mg/kg/infusion) showed some consistency during the initial weeks of testing which gradually declined or tended to decline to levels similar to that of the water control group during the later weeks of testing. Bupropion self-administration dose-dependently up-regulated DA transporters in caudate putamen and nucleus accumbens. In contrast, nomifensine self-administration did not alter DA transporter levels. These data provide evidence for heterogeneity among DA reuptake inhibitors, with some of these drugs being able to up-regulate DA transporters after their self-administration, whereas others lack this neuroadaptive response.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9103538&dopt=Abstract Bupropion Wellbutrin




Clin Pharmacol Ther. 1997 Apr;61(4):476-87.
Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline.

Modell JG, Katholi CR, Modell JD, DePalma RL.

Department of Psychiatry, University of Alabama at Birmingham School of Medicine 35294-0018, USA.

OBJECTIVE: To investigate patient reported prosexual side effects of the aminoketone antidepressant bupropion (INN, amfebutamone) and to compare directly the sexual side effects of bupropion and the selective serotonin reuptake inhibitor (SSRI) antidepressants fluoxetine, paroxetine, and sertraline. METHODS: One hundred seven psychiatric outpatient respondents receiving current treatment with one of the above antidepressants anonymously completed questionnaires that allowed reporting of both decreases and increases in sexual function. The main outcome measures were antidepressant-associated changes in libido, arousal, duration of time from arousal to orgasm, intensity of orgasm, and duration of orgasm relative to that experienced before the onset of the patients' psychiatric illnesses. RESULTS: Bupropion-treated patients reported significant increases in libido, level of arousal, intensity of orgasm, and duration of orgasm beyond levels experienced premorbidly. The three SSRIs to an equal degree significantly decreased libido, arousal, duration of orgasm, and intensity of orgasm below levels experienced premorbidly. Overall, 27% of the SSRI-treated patients had no adverse sexual side effects; in contrast, 86% of patients treated with bupropion had no adverse sexual effects, and 77% of bupropion-treated patients reported at least one aspect of heightened sexual functioning. CONCLUSIONS: SSRI-induced adverse sexual effects appear to be the rule rather than the exception and may be substantially underreported unless patients are specifically asked about the effects of these medications on various aspects of sexual function. In contrast, prosexual effects were reported by the majority of patients treated with bupropion. The findi




Psychopharmacology (Berl). 1997 Nov;134(2):201-12.
Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats.

Terry P, Katz JL.

Psychobiology Section, NIDA Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

Bupropion is a novel, non-tricyclic antidepressant with a primary pharmacological action of monoamine uptake inhibition. The drug resembles a psychostimulant in terms of its neurochemical and behavioural profiles in vivo, but it does not reliably produce stimulant-like effects in humans at clinically prescribed doses. Bupropion binds with modest selectivity to the dopamine transporter, but its behavioural effects have often been attributed to its inhibition of norepinephrine uptake. This experiment examines monoaminergic involvement in the discriminative stimulus effects of bupropion. Rats were trained to press one lever when injected i.p. with bupropion (17.0 mg/kg), and another lever when injected with saline. In substitution tests, dose-response curves were obtained for several monoamine uptake inhibitors. Nine of ten dopamine uptake blockers fully substituted for bupropion; the exception, indatraline (LU 19-005), partially substituted (71% bupropion-appropriate responding). Serotonin and norepinephrine uptake blockers (zimelidine and nisoxetine, respectively) produced negligible or limited substitution, and the anti-muscarinic dopamine uptake blocker benztropine produced limited partial substitution. A series of dopamine D1-like and D2-like receptor agonists were also tested: only the D2-like agonist RU 24213 fully substituted; three other D2-like agonists and four D1-like agonists partially substituted (50% < drug responding < 80%). Antagonism of the discriminative effects of bupropion was obtained with a D1- and a D2-like dopamine antagonist. The results demonstrate strong similarities with those obtained using other dopamine uptake inhibitors as training drugs, and support the view that the behavioural effects of bupropion are




J Clin Psychiatry. 1998 Mar;59(3):112-5.
Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction.

Ashton AK, Rosen RC.

State University of New York at Buffalo, School of Medicine, USA.

BACKGROUND: Serotonin reuptake inhibiting antidepressants (SRIs) are reported to cause sexual dysfunctions, including reduction in desire, arousal, and orgasm. This study evaluates the efficacy of bupropion in ameliorating sexual dysfunctions in patients receiving SRIs. METHOD: Forty-seven patients in an outpatient psychiatric practice who complained of SRI-induced sexual dysfunction accepted a trial of bupropion as an adjunct to their SRI, either as a p.r.n. or as a fixed-dose scheduled medicine. Patients received 75 mg or 150 mg of bupropion 1 to 2 hours before sexual activity. If this was insufficient to reduce their complaints, dose was increased gradually to 75 mg t.i.d. and sustained for 2 weeks. This regimen was then continued if successful. RESULTS: Bupropion successfully reversed a variety of sexual dysfunctions caused by SRIs in 31 (66%) of 47 patients. Fifty-two (69%) of 75 sexual complaints improved with bupropion treatment. The p.r.n. use of bupropion assisted 18 (38%) of 47 patients. Side effects of anxiety and tremor led to discontinuation of bupropion in 7 (15%) of 47 patients. Otherwise, bupropion was well tolerated. CONCLUSION: Bupropion administration may be a safe and effective method of treating SRI-induced sexual dysfunction. Placebo-controlled, double-blind studies are needed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9541153&dopt=Abstract Bupropion Wellbutrin