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The effects of desipramine and fluoxetine were examined on rat hepatic tryptophan-2,3-dioxygenase activity in the presence or absence of exogenous melatonin. Male Wistar rats were treated intraperitoneally over 8 days. The antidepressants were also administered individually and their impact on the enzyme noted. Desipramine reduced basal hepatic tryptophan-2,3-dioxygenase activity in the liver while fluoxetine had no observable effect. However, fluoxetine also prevented the hemin induced elevation in total enzyme activity. Exogenous melatonin (0.25mg/kg/day) for 8 days counteracted the inhibitory effects of both desipramine and fluoxetine at concentrations of 2.5mg/kg/day. Total enzyme activity was restored when melatonin was administered in combination with either drug. The experimental findings indicate that there is chemical antagonism at the surface of the enzyme between melatonin and the antidepressants that abolishes the observed inhibitory effects of the administered compounds.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9651108&dopt=Abstract
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ut.ee
The effects of acute antidepressant treatment were studied in the electric footshock and apomorphine-induced aggressiveness paradigms and found to be ineffective in both experimental models. In the apomorphine-induced aggressiveness test, 100 mg/kg L-tryptophan challenge manifested the antiaggressive effect of 10 mg/kg fluoxetine (a selective serotonin reuptake inhibitor) treatment. Thus, concomitant L-tryptophan plus fluoxetine treatment decreased the intensity of aggressive postures and increased the time of latency before first attack. In conclusion, our study demonstrates the involvement of the serotoninergic neurotransmission in the neurobiology of aggressive behavior, but after acute treatment in normal rats, the antidepressants do not elicit antiaggressive effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9658383&dopt=Abstract
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Drug Metab Dispos. 1998 Jul;26(7):617-22.
Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women.
Allard S, Sainati S, Roth-Schechter B, MacIntyre J.
Lorex Pharmaceuticals, Chicago, IL 60680-5110, USA.
The objective was to evaluate possible pharmacokinetic and pharmacodynamic interactions for repeated nightly zolpidem dosing with fluoxetine. Twenty-nine healthy female volunteers (mean age, 25. 6 years) received zolpidem (10 mg) and fluoxetine (20 mg) in the following open design: zolpidem on night 1 followed by 1 washout day, a daily morning dose of fluoxetine on days 3 through 27, and a morning dose of fluoxetine plus an evening dose of zolpidem on days 28 through 32. Plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined at the transitions from one regimen to the next. Morning psychomotor tests were performed on days 1, 2, 28, 29, and 33. Steady-state plasma concentrations of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. No significant differences in any pharmacokinetic parameters for fluoxetine and norfluoxetine were observed between day 27 and day 32. There were no significant differences in AUC, maximal plasma concentration, or time to maximal concentration parameters for zolpidem plasma concentrations among nights 1, 28, and 32. There was a statistically significantly increased t1/2 for zolpidem on night 32, compared with night 28 (3.64 and 3.29 hr, respectively). There were no significant differences in the next-morning Digit Symbol Substitution Test performance at any time in the study. Both zolpidem and fluoxetine were well tolerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic interactions between fluoxetine and zolpidem (five consecutive doses) when the drugs are coadministered to healthy women. Therefore, based on these observations, short-term cotherapy with fluoxetine (20 mg) and zolpidem (10 mg) appears safe.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9660843&dopt=Abstract
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