Drugs online research references
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 primarily mediated by dopaminergic mechanisms.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9399385&dopt=Abstract
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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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9541153&dopt=Abstract
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Psychopharmacology (Berl). 1998 Mar;136(2):190-7.
Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test.
Reneric JP, Lucki I.
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-2648, USA.
Because of clinical interest in the effects of antidepressant drugs that exert their effects on multiple neurotransmitter systems, the behavioral effects produced by combined treatment with an SSRI (fluoxetine) with a selective norepinephrine (NE; desipramine) or dopamine (DA) reuptake inhibitor (buproprion) were examined in the forced swimming test (FST), a behavioral test in rodents that predicts the clinical activity of antidepressants. Three additional compounds with mixed activity as NE-5-HT reuptake inhibitors, milnacipran, duloxetine and venlafaxine, were also examined. Desipramine and fluoxetine both reduced immobility in the FST, but desipramine increased only climbing behavior, whereas fluoxetine increased only swimming behavior. The combination of fluoxetine with desipramine or bupropion increased both climbing and swimming behaviors at certain doses, but higher doses of desipramine when combined with fluoxetine replaced swimming behavior with climbing behavior. The mixed NE-5-HT reuptake inhibitors milnacipran and duloxetine reduced immobility and increased climbing behavior, but did not alter swimming. Venlafaxine reduced immobility and increased swimming behavior, except at the highest dose tested (80 mg/kg), which increased both swimming and climbing behaviors. Thus, combining certain doses of pharmacologically selective monoamine reuptake inhibitors, or the mixed reuptake inhibitor venlafaxine, produced a pattern of mixed active behaviors in the FST (climbing and swimming) that may reflect the activity of multiple neurotransmitters, especially the combination of enhanced 5-HT and DA activity. The combination of higher doses of desipramine with fluoxetine, or compounds with mixed activity at inhibiting NE and 5-HT reuptake, demonstrated effects similar to those of desipramine alone and may reflect inhibition of the expression of serotonergic antidepressant behavioral effects by selective NE reuptake inhibitors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9551776&dopt=Abstract
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