J Neurosci Res. 1994 Sep 1;39(1):11-22.
Dopamine transporter mediated release of dopamine: role of chloride.

Sitges M, Reyes A, Chiu LM.

Division de Investigaciones Clinicas, Instituto Mexicano de Psiquiatria, SSA, Mexico.

Using a rapid (0.5 ml/min) flow rate superfusion system, the dopamine (DA) transporter mediated release of DA is further explored, and compared to the depolarization evoked release of DA in rat striatal synaptosomes preloaded with radioactive DA (3H-DA). In this system external DA in the low microM range efficaciously releases the preloaded transmitter, the maximal response being reached at 3 microM DA. The external DA stimulated release is Ca(2+)-independent, Cl(-)-dependent, and blocked by both bupropion and nomifensine. The atypical antidepressant bupropion inhibits 3H-DA accumulation to rat striatal synaptosomes with a calculated IC50 of 1.3 x 10(-6) M. Among DA uptake blockers some are known to act as DA releasing agents. Here we found that the DA uptake blocker nomifensine (30 microM) is unable to modify the baseline release of 3H-DA, whereas bupropion (10 microM) clearly elevates the baseline release of 3H-DA in a Ca(2+)-independent and Cl(-)-dependent manner. The non releasing agent nomifensine blocks the release of 3H-DA induced by bupropion. The Ca(2+)-dependent, high K+ depolarization evoked release of 3H-DA is not modified by nomifensine and does not depend on the external Cl- concentration. When the depolarizing medium contains DA the carrier mediated release of 3H-DA induced by the external DA is additive to the high K+ induced response. A drastic drop in the external Cl- concentration induces 3H-DA release. This release of 3H-DA induced by low external Cl- levels is completely blocked by nomifensine, which only slightly diminished the release of 3H-DA induced by the absence of external Na+. On the basis of these results, it is concluded that: 1) Rapid perfusion flow rates eliminate DA reuptake. 2) DA uptake inhibitors either with or without DA releasing cap




Neuropsychopharmacology. 1994 Oct;11(2):133-41.
Evidence that the acute behavioral and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism.

Cooper BR, Wang CM, Cox RF, Norton R, Shea V, Ferris RM.

Division of Pharmacology Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.

Bupropion (BW 323U66) has been considered a dopaminergic antidepressant based on its ability to inhibit the uptake of dopamine (DA) somewhat more selectively than it inhibits uptake of norepinephrine (NE) or serotonin (5-HT). This report describes new evidence that bupropion selectively inhibits firing rates of NE cells in the locus coeruleus (LC) at doses significantly lower than those that inhibit activity of midbrain DA cells or dorsal raphe 5-HT cells. The IC50 dose (13 mg/kg i.p.) for inhibition of LC firing produced plasma concentrations that were not significantly different from those generated by the ED50 in the Porsolt test (10 mg/kg i.p.). The fourfold higher dose needed to inhibit DA cell firing (IC50 = 42 mg/kg i.p.) was similar to the dose associated with locomotor stimulation in freely moving rats. Bupropion did not change the firing rates of 5-HT cells in the dorsal raphe nucleus at any dose. In both in vitro and in vivo tests, the metabolite 306U73 (hydroxybupropion), a weak inhibitor of NE uptake, was approximately equipotent to bupropion with regard to inhibition of LC cells. Another metabolite, 494U73, had no effect on LC firing rates over a wide range of doses. Because of species variation in metabolism, 306U73 was not detected in plasma of rats after i.v. doses of bupropion that inhibited LC firing. Only trace amounts of 306U73 were detected after bupropion dosing for the Porsolt test. Pretreatment with reserpine markedly depleted catecholamines and reduced (by 30-fold) the potency of bupropion to inhibit LC firing.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7840865&dopt=Abstract Bupropion Wellbutrin




J Recept Res. 1993;13(1-4):341-54.
Regulation of dopamine receptors by bupropion: comparison with antidepressants and CNS stimulants.

Vassout A, Bruinink A, Krauss J, Waldmeier P, Bischoff S.

Research Department, CIBA-GEIGY Ltd., Basel, Switzerland.

Acute treatment of rats with the antidepressant bupropion increased [3H]spiperone binding to D2 receptors in vivo. This dose- and time-dependent effect was greatest in striatum and minimal in cerebellum and pituitary. A parallel behavioral stimulation occurred in the same rats. Among 21 antidepressants and CNS stimulants tested, only those that activate dopamine (DA) transmission had similar effects: nomifensine, amineptine, methylphenidate, D-amphetamine, amfonelic acid, cocaine, benztropine and GBR 12909. Decreasing DA transmission with reserpine plus alpha-methyl-p-tyrosine prevented the action of bupropion. Finally, bupropion was inactive in vitro and ex-vivo. Therefore, we propose that bupropion and other DA-enhancing agents modify the characteristics of [3H]spiperone binding through the intervention of a dynamic regulation of the D2 receptors by the neurotransmitter itself.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8095555&dopt=Abstract Bupropion Wellbutrin




J Clin Psychiatry. 1993 Dec;54(12):459-65.
Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion.

Walker PW, Cole JO, Gardner EA, Hughes AR, Johnston JA, Batey SR, Lineberry CG.

Department of Psychiatry, University of Tennessee, Memphis.

BACKGROUND: This study was conducted to determine the effect of bupropion on the sexual functioning of male and female outpatients who developed anorgasmia or delayed orgasm while receiving fluoxetine treatment for depression. METHOD: Thirty-nine patients who satisfied criteria for participation in the study discontinued fluoxetine treatment and entered a 2-week washout phase followed by an open 8-week bupropion treatment phase. Three parameters of sexual functioning were followed throughout the study: orgasm function, libido, and satisfaction with overall sexual functioning. Depression was also evaluated at each visit. RESULTS: All patients reported orgasm delay and/or failure at the time of fluoxetine discontinuation. Orgasm function, libido, and satisfaction with sexual functioning improved during the 2-week fluoxetine washout period and during the bupropion treatment phase. Ninety-four percent of patients (29/31) had complete or partial resolution of their orgasm dysfunction at the end of bupropion treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied with their overall sexual functioning. Most patients entered the study with decreased libido on fluoxetine. Libido was "much" or "very much" increased for 81% of patients (25/31) at the end of the study. In addition, depression scores on the Hamilton Rating Scale for Depression and Clinical Global Impressions-Severity scale significantly improved during the bupropion treatment phase. Finally, bupropion was well tolerated by most patients. CONCLUSION: Bupropion may be an appropriate antidepressant for patients who develop sexual dysfunction during fluoxetine treatment or for whom sexual dysfunction is a conce




Arzneimittelforschung. 1996 Jul;46(7):667-9.
Different effects of the antidepressant drugs imipramine, maprotiline and bupropion on insulin secretion from mouse pancreatic islets.

el-Dakhakhny M, Abdel el-Latif HA, Ammon HP.

Pharmacology Department of Alexandria Medical Faculty, Alexandria, Egypt.

In some previous studies, acute administration of some antidepressants has been reported to cause significant changes in the levels of blood glucose and insulin in the rabbit. In the present study the effects of several antidepressants representing classical groups of antidepressants, namely imipramine (CAS 50-49-7, I), maprotiline (CAS 10347-81-6, M) and bupropion (CAS 34911-55-2, (B) on insulin secretion from the isolated islets of Langerhans in mice was studied. Maprotiline and bupropion stimulated insulin release, while imipramine was without any effect in presence of 8.3 mmol/l glucose. On the other hand, in presence of 16.7 mmol/l imipramine and maprotiline suppressed the stimulated insulin secretion. Bupropion inversely significantly stimulated the insulin secretion in presence of 16.7 mmol/l glucose. It is concluded that the changes of blood glucose and plasma insulin observed in vivo may at least in part be due to respective changes of insulin secretion. The treatment of diabetic patients receiving antidepressant drugs with hypoglycaemic agents should be taken in consideration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8842333&dopt=Abstract Bupropion Wellbutrin