An in vitro evaluation of fluoxetine adsorption by activated charcoal and desorption upon addition of polyethylene glycol-electrolyte lavage solution. Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors. Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test. Rx drugs

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J Toxicol Clin Toxicol. 1998;36(1-2):117-24.
An in vitro evaluation of fluoxetine adsorption by activated charcoal and desorption upon addition of polyethylene glycol-electrolyte lavage solution.

Atta-Politou J, Kolioliou M, Havariotou M, Koutselinis A, Koupparis MA.

University of Athens, Greece.

BACKGROUND: In drug overdoses, treatment with activated charcoal is frequently used because of its adsorptive properties. Recently, whole-bowel irrigation with polyethylene glycol-electrolyte lavage solution has been used as a gastrointestinal decontamination procedure for ingestions of toxins not well adsorbed to activated charcoal and for toxins with a delayed absorption phase, although well adsorbed to activated charcoal. While a combined approach using activated charcoal and whole-bowel irrigation could theoretically enhance the efficacy of both modalities, this improvement remains speculative, since data demonstrating its clinical advantage in overdose treatment are lacking. Fluoxetine, a selective serotonin uptake inhibitor, is one of the most frequently prescribed antidepressants. Fluoxetine is well adsorbed onto activated charcoal. This in vitro investigation was undertaken to study: a) the effect of polyethylene glycol, as well as polyethylene glycol-electrolyte lavage solution, on the adsorption of fluoxetine to laboratory grade-activated charcoal and a commercial activated charcoal formulation (Carbomix powder) in simulated gastric (pH= 1.2) and intestinal (pH=7.2) fluid environment; b) whether the order of polyethylene glycol-electrolyte lavage solution addition would have any effect on the adsorption of fluoxetine to activated charcoal. METHODS: Adsorption of fluoxetine to charcoal in the presence of polyethylene glycol was examined: a) by the simultaneous addition of polyethylene glycol and charcoal to fluoxetine solution and b) by the addition of charcoal to fluoxetine solution and subsequent addition of polyethylene glycol. In both cases, the slurries were incubated at 37 degrees C for 1 hour and filtered. Free fluoxetine concentration was determined in the diluted filtrate by a reversed-phase high-performance liquid chromatography method. RESULTS: The amount of fluoxetine adsorbed to activated charcoal (or Carbomix) was dramatically decreased at gastric and intestinal pH by the presence of polyethylene glycol or polyethylene glycol-electrolyte lavage solution added either concurrently or sequentially to activated charcoal. CONCLUSIONS: In cases of fluoxetine overdose, administration of activated charcoal is recommended, while a combined approach using activated charcoal and whole-bowel irrigation with polyethylene glycol-electrolyte lavage solution is not recommended since it causes a significant desorption of the drug from activated charcoal.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9541057&dopt=Abstract

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Eur J Pharmacol. 1998 Jan 26;342(2-3):367-70.
Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors.

Nowak G, Legutko B, Skolnick P, Popik P.

Institute of Pharmacology, Polish Academy of Sciences, Smetna, Krakow.

Glycine displaces [3H]CGP-39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) binding to the glutamate recognition site with both high and low affinity. We reported previously that chronic treatment with antidepressants reduced the proportion of high to low affinity sites, or, even eliminated the high affinity sites in case of citalopram. Here, we compared the effects of citalopram with another serotonin specific reuptake inhibitor, fluoxetine on this measure. Chronic administration of citalopram or fluoxetine eliminated high affinity glycine-displaceable [3H]CGP-39653 binding to the mouse cortex in 78 and 56% of animals, respectively, indicating that selective serotonin reuptake inhibitors produce qualitatively similar adaptive changes at NMDA receptors, that differ from other antidepressants in this neurochemical measure.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9548410&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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