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J Neurochem. 1988 Oct;51(4):1060-9.
Differentiation of dopamine overflow and uptake processes in the extracellular fluid of the rat caudate nucleus with fast-scan in vivo voltammetry.
May LJ, Kuhr WG, Wightman RM.
Department of Chemistry, Indiana University, Bloomington 47405.
Stimulated overflow of dopamine (DA) into the extracellular fluid of the rat caudate nucleus was measured with fast-scan cyclic voltammetry. DA concentrations were sampled in less than 10 ms at 100-ms intervals with a Nafion-coated, carbon-fiber microelectrode. Overflow of DA was induced by electrical stimulation of the medial forebrain bundle with 300-microA pulses of various duration and frequency. Stimulated overflow was measured as a function of stimulus duration before and after administration of benztropine, bupropion, and amphetamine. These results were correlated with simulated curves based on a simple uptake/overflow model. The observed overflow was assumed to be a function of [DA]p, the concentration of DA which overflows per stimulus pulse, and the kinetics of cellular uptake of DA. Correlation of experimental with stimulated results was obtained at the 95% confidence limit for the duration studies; however, it was not possible to distinguish between the effects of pharmacological agents on uptake and overflow. In contrast, modulation of stimulus frequency did permit such distinction. Simulations of an increase in [DA]p fit results following dihydroxyphenylalanine methyl ester at 95% confidence limits, whereas an equivalent change in the apparent Km did not fit. An increase in the apparent value of Km correlated with results obtained at different frequencies following nomifensine and bupropion administration at the 95% confidence limit, whereas an equivalent increase in [DA]p did not fit. The effects of GBR 12909 best correlated with an increase in the DA available for overflow.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2971098&dopt=Abstract
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J Clin Psychiatry. 1983 May;44(5 Pt 2):143-7.
Private practice evaluation of the safety and efficacy of bupropion in depressed outpatients.
Kirksey DF, Harto-Truax N.
A multicenter uncontrolled 4-week trial of bupropion in depressed outpatients was conducted in the private practices of 25 internists, 9 family practitioners, and 3 psychiatrists. Minimum exclusion criteria were used with respect to concurrent medical ailments, age, and concomitant medications. Of the 380 patients admitted to the study, 325 were included in efficacy analyses, and 359 provided data for safety analyses. The average patient was a 51-year-old married white woman with a high school education and a skilled job. Bupropion administered in doses of 150-450 mg/day was highly effective in reducing depressive symptomatology as evaluated by the Hamilton Depression and Clinical Global Impressions scales, and the Zung Self-Rating Scale. No clinically significant bupropion-related changes in blood pressure, pulse rates, respiration rate, body temperature, or laboratory parameters were recorded; only 41 patients were discontinued due to intolerance to adverse experiences. There was a notable absence of daytime sedation, and of anticholinergic and cardiovascular side effects.
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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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6768086&dopt=Abstract
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