Farmakol Toksikol. 1988 Jan-Feb;51(1):14-7.
[Bupropion activation of memory trace retrieval in amnesia and forgetting]

[Article in Russian]

Il'iuchenok RIu, Dubrovina NI, Vinnitskii IM.

The effect of a new antidepressant bupropion on the processes of retrieval of the conditioned response of passive avoidance in mice under amnesia of different genesis and spontaneous forgetting was studied. The drug was shown to exert the antiamnesic effect and to facilitate retrieval of amnesia-affected or forgotten memory trace. The maximal effect of bupropion was observed at the dosage of 30 mg/kg. At the use of bupropion on the 2nd day after exertion of amnesic influences there was registered the tendency to prolongation of preservation of the conditioned habit enhanced retrieval as compared with greater time periods. The drug effect under memory trace retrieval impaired by cycloheximide-induced amnesia was similar in the action but more pronounced than that under "psychogenic" amnesia. The data obtained testify in favour of an active involvement of the brain dopaminergic system in the processes of memory trace retrieval.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3129303&dopt=Abstract Bupropion Wellbutrin




Eur J Drug Metab Pharmacokinet. 1988 Jul-Sep;13(3):149-53.
Effect of hepatic and renal dysfunction on disposition of bupropion in rats.

Kaka JS, Al-Khamis KI, Tanira MO.

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Disposition of bupropion after oral administration was investigated in carbon tetrachloride (CCl4) and gentamicin treated rats. Bupropion exhibits extensive first-pass effect and is mainly cleared by hepatic route. In rats with hepatic damage, maximum plasma concentration (Cmax) was approximately 3 times higher and area under the plasma concentration-time curve up to 6 h (AUC 0-6) and AUC 0-infinity increased on an average 4 and 5 times respectively compared to the control. The half-life was doubled with hepatic dysfunction. These findings suggest that hepatic impairment in rats causes a decrease in first pass effect as well as an increase in the half-life of the drug. Rats with renal impairment, exhibited a significant increase in Cmax, AUC 0-6 and AUC 0-infinity of bupropion approximately 3-fold as compared to the control, no change in half life of the drug was observed. This indicates that rats with renal impairment show less efficient first-pass effect which may lead to increase in systemic bioavailability. The time to peak observed in all treated animals was not significantly different from the control. The percentage of bound bupropion did not differ either in CCl4 or gentamicin treated plasma as compared to the control.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3149241&dopt=Abstract Bupropion Wellbutrin




Eur J Clin Pharmacol. 1985;29(1):97-103.
The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses.

Posner J, Bye A, Dean K, Peck AW, Whiteman PD.

The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3932079&dopt=Abstract Bupropion Wellbutrin




Life Sci. 1985 Nov 25;37(21):2021-7.
The conditioned place preference paradigm in rats: effect of bupropion.

Ortmann R.

The effect of bupropion in the conditioned place preference paradigm in rats is described. In doses between 10 and 50 mg/kg i.p. bupropion increased the time rats spent in a shuttle box compartment conditioned to this compound. This effect of bupropion was not blocked by pretreatment of the animals with 0.1 mg/kg i.p. haloperidol or 50 mg/kg i.p. sulpiride. The same doses of the neuroleptics did, however, attenuate locomotor hyperactivity induced by bupropion. Bupropion thus seems to belong to the group of CNS stimulants whose effect in the conditioned place preference paradigm is not blocked by neuroleptics.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3934485&dopt=Abstract Bupropion Wellbutrin




Pol J Pharmacol Pharm. 1985 May-Jun;37(3):243-52.
Central effects of repeated treatment with bupropion.

Klimek V, Nowak G, Czyrak A.

The effect of bupropion, a new clinically active antidepressant drug, administered repeatedly to rats and mice, was compared with that of imipramine. The drugs were given orally twice a day for 14 days, bupropion in a dose of 20 mg/kg, imipramine--10 mg/kg. The action of bupropion was studied in the following tests: clonidine-induced aggression in mice, open field in rats, amphetamine-induced hypermotility in rats, clenbuterol-induced hyperthermia in rats kept at high ambient temperature. Moreover, the effect of bupropion on 3H-prazosin binding to membranes from the cerebral cortex was measured. On the basis of the results obtained it may be concluded that in some tests chronically administered bupropion acts like imipramine; as both drugs potentiate the amphetamine-enhanced locomotor activity, attenuate the hyperthermic response to clenbuterol and increase the number of 3H-prazosin binding sites in the cerebral cortex.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3934652&dopt=Abstract Bupropion Wellbutrin