Determination of fluoxetine in human plasma using reserved phase HPLC. Blockade of pre- and post-synaptic 5-HT1A receptors does not modify the effect of fluoxetine or 5-hydroxytryptophan on ethanol and food intake in rats. Alterations in behavior and opioid gene expression induced by the novel tropane analog WF-31. Rx drugs

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Pharmazie. 1997 Nov;52(11):854-6.
Determination of fluoxetine in human plasma using reserved phase HPLC.

Misztal G, Hopkala H.

Department of Medicinal Chemistry, Medical Academy, Lublin, Poland.

A rapid, simple, accurate method for the determination of fluoxetine in human plasma is presented. Liquid-liquid extraction of fluoxetine was carried out using diethyl ether. Chlorprothixene was applied as an internal standard. The samples were chromatographed on a LiChrosorb RP-18 (10 microns) column and the mobile phase was acetonitrile/phosphate buffer pH 2.70 (9:1). The detection was carried at 254 nm. A linear quantitative response curve was generated over a concentration range of 100-600 ng/ml. Overall extraction efficiency of the extraction procedure was found to be 86 to 91% with a correlation coefficient of 0.992.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9399342&dopt=Abstract

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Psychopharmacology (Berl). 1997 Nov;134(1):55-63.
Blockade of pre- and post-synaptic 5-HT1A receptors does not modify the effect of fluoxetine or 5-hydroxytryptophan on ethanol and food intake in rats.

Ciccocioppo R, Panocka I, Polidori C, Dourish CT, Massi M.

Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy.

Selective serotonin reuptake inhibitors (SSRIs) or serotonin precursors inhibit ethanol and food intake by increasing the synaptic availability of 5-HT in the central nervous system. However, these agents can also increase 5-HT levels at somatodendritic 5-HT1A autoreceptors, with negative effects on serotonergic transmission. (+)WAY100135 [N-ter-butyl 3-4-(2-methoxy-phenyl) piperazin-1-yl-2-phenylpropanamide dihydrochloride] is a selective antagonist both at pre- and post-synaptic 5-HT1A receptors. The present study investigated the effect on ethanol and food intake of (+)WAY100135, given alone or coadministered with the SSRI fluoxetine or the 5-HT precursor 5-hydroxytryptophan (5-HTP) in genetically selected alcohol-preferring rats. Blockade of presynaptic 5-HT1A receptors after injection of (+)WAY100135, 0.1 or 1 microgram/rat, into the dorsal raphe did not significantly modify ethanol, food or total fluid intake. The same doses of (+)WAY100135 did not modify the inhibition of ethanol and food intake induced by intraperitoneal (i.p.) injection of fluoxetine, 5 mg/kg. Subcutaneous (s.c.) administration of (+)WAY100135 (1 or 10 mg/kg) did not affect the 3-h, or the overnight intake of ethanol, food or total fluids. Given together with i.p. fluoxetine (5 mg/kg) or s.c. 5-HTP (100 mg/kg plus carbidopa. 12.5 mg/kg), the same s.c. doses of (+)WAY100135 did not modify their inhibitory effect on ethanol and food consumption. Present findings suggest that blockade either of pre- or of pre- and postsynaptic 5-HT1A receptors does not potentiate the inhibitory effect of fluoxetine or 5-HTP on ethanol and food intake.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9399367&dopt=Abstract

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Brain Res Mol Brain Res. 1997 Oct 15;50(1-2):293-304.
Alterations in behavior and opioid gene expression induced by the novel tropane analog WF-31.

Daunais JB, Hart SL, Hedgecock-Rowe A, Matasi JJ, Thornley C, Davies HM, Porrino LJ.

Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1083, USA.

The effects of the acute administration of the serotonin-selective tropane analog, [2beta-propanoyl-3beta-(4-isopropylphenyl)-tropane, WF-31, on spontaneous locomotor activity were measured and compared to those of the highly selective serotonin uptake inhibitor, fluoxetine and cocaine, a non-selective re-uptake inhibitor of dopamine and serotonin. WF-31 (1, 10 and 30 mg/kg)-elicited increases in locomotor behaviors when compared to vehicle-treated rats. This increased activity was blocked by pre-treatment with the dopaminergic antagonist, flupenthixol, suggesting that these effects may be mediated by dopaminergic mechanisms. Cocaine, but not fluoxetine, also elicited increases in behaviors. In addition, the effects of these three compounds on opioid peptide gene expression were also assessed using in situ hybridization histochemistry in the same animals. The acute administration of both WF-31 and cocaine increased the expression of preprodynorphin mRNA in the dorsal striatum whereas fluoxetine had no effect. Expression of striatal preproenkephalin mRNA was augmented by all three compounds. Within the nucleus accumbens, PPD mRNA levels were affected only by treatment with WF-31, an effect that was blocked by pre-treatment with flupenthixol. In contrast, the acute administration of both WF-31 and fluoxetine, but not cocaine, increased the expression of preproenkephalin mRNA. These increases, however, were not reversed by pre-treatment with flupenthixol. Despite its profile in vitro as a relatively selective serotonin re-uptake inhibitor, some of the in vivo actions of WF-31 appear to be mediated by dopaminergic mechanisms. These data further suggest that the mechanisms underlying expression of the opioid peptides in the nucleus accumbens may vary from those in the dorsal striatum.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9406946&dopt=Abstract

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