Drugs online research references
Synapse. 1991 Sep;9(1):27-34.
Comparative analysis of the effects of iontophoretically applied dopamine in different regions of the rat brain, with special reference to the cingulate cortex.
Beauregard M, Ferron A, Descarries L.
Departement de Physiologie, Faculte de Medecine, Universite de Montreal, Quebec, Canada.
A systematic comparison of the effects of iontophoresed dopamine (DA) was carried out in the neostriatum (NS), nucleus accumbens (Acb) and anterior cingulate (ACg), prefrontal (PF) and parietal (Par) cortex of urethane-anesthetized rats, before and after treatment with the specific DA uptake blockers GBR 12909 and Bupropion. Similar experiments were also conducted after DA denervation with 6-hydroxydopamine and after DA depletion with alpha-methyl-p-tyrosine. The average rate of spontaneous neuronal firing was comparable in all regions, except in the NS after DA depletion. A majority of the units were inhibited by DA in every region and condition tested. As assessed with the IT50 index, the responsiveness to DA was not markedly different between regions, indicating that the postsynaptic sensitivity to this amine is independent of the density of DA receptors and of DA innervation. In contrast, the average duration of DA inhibitions (RT90) was considerably longer (5-fold) in the intact ACg than in the PF, Par, NS, or Acb. Moreover, treatment with both DA uptake blockers reduced the duration of DA inhibitions in ACg (4- to 9-fold); while lengthening it in PF, NS and Acb; and having no apparent effect in Par. DA depletion and DA denervation also reduced the duration of the DA inhibitions in ACg without effect in Par. Taken together, these results provide further evidence for the existence of a presynaptic, positive-feedback mechanism in ACg, triggered by DA, and favouring the further release of this transmitter upon its reuptake in DA nerve terminals.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1839089&dopt=Abstract
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Psychopharmacology (Berl). 1986;89(4):404-8.
The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs.
DeVane CL, Laizure SC, Cameron DF.
Dosage regimen adjustments because of poor renal function are often assumed to be unnecessary for extensively metabolized antidepressants. This assumption is being increasingly questioned in recognition of the role of active drug metabolites. The purpose of this study was to assess the steady-state accumulation of the new antidepressant bupropion and its three major basic metabolites in guinea pigs, with and without experimentally-induced renal failure. Two groups of guinea pigs were treated by intraperitoneal (IP) implantation of mini-osmotic pumps containing bupropion hydrochloride. Immediately after surgery, one group of animals received an injection of uranyl nitrate. After 4 days, all animals were sacrificed by decapitation following blood removal by cardiac puncture. Analysis of plasma and brain samples by high performance liquid chromatography (HPLC) for concentrations of bupropion (BUP) and its major basic metabolites, the erythro-amino alcohol (EB), the threo-amino alcohol (TB) and the hydroxy metabolite (HB) revealed greater accumulation of BUP, TB, and HB in plasma and brain of the animals with renal failure compared to controls. No difference was found between groups in the concentrations of the EB metabolite. As the guinea pig shows a BUP and metabolite plasma concentration profile similar to that seen in human studies, these results suggest that further studies of bupropion and its major metabolites are warranted in patients with impaired renal function to assess possible excessive drug and metabolite accumulation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3092270&dopt=Abstract
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Biol Psychiatry. 1992 Nov 1;32(9):834-8.
Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome.
Goodnick PJ, Sandoval R, Brickman A, Klimas NG.
Department of Psychiatry, University of Miami, Florida 33136.
Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion. In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01). Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1450297&dopt=Abstract
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