Prozac
Accumulation of fluoxetine and norfluoxetine in human brain during therapeutic administration.

Renshaw PF, Guimaraes AR, Fava M, Rosenbaum JF, Pearlman JD, Flood JG, Puopolo PR, Clancy K, Gonzalez RG.

MGH-NMR Center, Massachusetts General Hospital-East, Charlestown.

In vivo 19fluorine nuclear magnetic resonance spectroscopy was used to measure the brain concentration of fluoxetine and norfluoxetine in five patients with obsessive-compulsive disorder and three with major depression. The mean brain:plasma ratio of the parent drug plus the metabolite was significantly elevated to 2.6 (SD = 1.0) (95% confidence interval = 1.9-3.3). This accumulation may have implications for understanding both the therapeutic and the toxic effects of fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1415832&dopt=Abstract fluoxetine Prozac



Prozac
Effects of fluoxetine administration on regional galanin expression in obese Zucker rat hypothalamus.

Churruca I, Portillo MP, Gutierreza A, Casis L, Macarulla MT, Zarate J, Echevarria E.

Department of Nutrition and Food Science, University of the Basque Country, Paseo de la Universidad 7, 01006 Vitoria, Spain.

The aim of the present work was to study the potential involvement of hypothalamic galanin system in the anorectic mechanism of fluoxetine in obese Zucker rats. Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. Significant decreases in food intake, final body weight and total body fat were observed after fluoxetine treatment. Although fluoxetine-treated rats showed a decrease in urine elimination, this effect was not enough to compensate decreased water intake, leading to dehydration, as showed by decreased body water content. Chronic fluoxetine administration increased the numbers of galanin positively immunostained neural cells in medial and lateral preoptic areas, lateral hypothalamic area and paraventricular nucleus (rostral and magnocellular regions), without changes in dorsomedial, ventromedial, supraoptic, suprachiasmatic and arcuate nuclei. Taken into account that galanin stimulates appetite, these results could represent rather a compensatory response against reduced food intake than a direct anorectic mechanism. Changes in the magnocellular region of the hypothalamic paraventricular nucleus suggest a role for galanin neural circuits at this level in fluoxetine-induced hydro-osmotic impairment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15526991&dopt=Abstract fluoxetine Prozac



Prozac
High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine.

Fava M, Rosenbaum JF, Cohen L, Reiter S, McCarthy M, Steingard R, Clancy K.

Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114.

In a four-week, open label study of major depression, 15 patients who had failed to respond to a trial of fluoxetine 20 mg/day of 8-12 weeks duration were then treated with fluoxetine 40 mg/day for one week and then, if tolerated, with either 60 or 80 mg/day. The mean HAM-D-17 and CGIS scores of these 15 patients decreased significantly at the end of 4 weeks on a higher dosage of fluoxetine (60 or 80 mg/day) with respect to the beginning of the four-week study. No significant side-effects were noted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1430659&dopt=Abstract fluoxetine Prozac



Prozac
Ethanol intake of chickens treated with fenfluramine, fluoxetine, and dietary tryptophan.

Lu MR, Wagner GC, Fisher H.

Department of Nutritional Sciences, Rutgers State University of New Jersey, New Brunswick 08903-0231.

Male, white leghorn chickens fed a standard diet with or without tryptophan supplementation were treated with single injections of 8 mg/kg fenfluramine in one series of experiments, or 8 mg/kg fluoxetine in another series. The birds had been food- and water-deprived prior to injection. They were offered, following the drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 hr. Both fluoxetine and fenfluramine significantly reduced consumption of the ethanol solution, an effect exacerbated by tryptophan supplementation. Water or sucrose solution intake was also significantly reduced, but significantly less so than ethanol after fenfluramine injection. Since the birds drank significantly more of the sucrose solution after saline injection than of water, the consumption decrease caused by fenfluramine resulted, nevertheless, in a higher intake than that of either water or ethanol. Body temperature was decreased by ethanol intake and/or fluoxetine injection. Fenfluramine injection had an opposite, body temperature-increasing effect. It appears that both fenfluramine and fluoxetine decrease ethanol intake in a manner more specific than for water or sucrose, and that this effect is amplified by dietary tryptophan supplementation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1443420&dopt=Abstract fluoxetine Prozac



Prozac
Simultaneous determination of fluoxetine and norfluoxetine enantiomers in biological samples by gas chromatography with electron-capture detection.

Torok-Both GA, Baker GB, Coutts RT, McKenna KF, Aspeslet LJ.

Department of Psychiatry, University of Alberta, Edmonton, Canada.

An electron-capture gas chromatographic procedure was developed for the simultaneous analysis of the enantiomers of fluoxetine and norfluoxetine. The assay involves basic extraction of these enantiomers from the biological samples, followed by their conversion to diastereoisomers using the chiral derivatizing reagent (S)-(-)-N-trifluoroacetylprolyl chloride. The method was utilized to detect and measure the quantity of these enantiomers in plasma and urine of patients and in liver and brain tissue of rats treated with (R,S)-fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1447355&dopt=Abstract fluoxetine Prozac



Prozac
Adverse cutaneous reactions associated with fluoxetine strategy for reintroduction of this drug in selected patients.

Leznoff A, Binkley KE, Joffee RT, Levitt A, Richter MA.

Department of Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.

Four patients treated with fluoxetine alone developed generalized urticaria. One also suffered polyarthritis. These reactions subsided when fluoxetine was stopped. After 6-12 months, because of progressive psychiatric problems, fluoxetine was reintroduced using a desensitization protocol. In each case this was well tolerated, and fluoxetine has been continued without adverse affects for 3-10 months.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1479054&dopt=Abstract fluoxetine Prozac



Prozac
Fluoxetine hydrochloride enhances in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

Gerena L, Bass GT Sr, Kyle DE, Oduola AM, Milhous WK, Martin RK.

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

The emergence of chloroquine resistance in Plasmodium falciparum has necessitated the development of alternate strategies for chemotherapy and chemoprophylaxis. One approach has been the identification of drugs that do not possess any intrinsic antimalarial activity when used alone but that potentiate the effect of currently available antimalarial drugs, such as chloroquine. We identified fluoxetine hydrochloride (Prozac), a commonly prescribed antidepressant, as another resistance modulator for drug-resistant P. falciparum. Studies with chloroquine-resistant clones and isolates from various geographical locations confirmed our initial observations with a chloroquine-resistant P. falciparum clone, W2. Fluoxetine concentrations of 500 nM were found to effectively modulate chloroquine resistance by 66% in clone W2. In comparison, verapamil at similar concentrations was observed to modulate chloroquine resistance in clone W2 by 61%. Neither fluoxetine nor verapamil was observed to possess any innate antimalarial activity. These data augment the current description of the chloroquine resistance phenotype and may provide additional insights into lead-directed synthesis of new antimalarial drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1482144&dopt=Abstract fluoxetine Prozac



Prozac
Hypericum extract LI 160 and fluoxetine in mild to moderate depression A randomized, placebo-controlled multi-center study in outpatients.

Bjerkenstedt L, Edman GV, Alken RG, Mannel M.

Dept. of Clinical Neuroscience, Psychiatry Section Karolinska Hospital, 17176, Stockholm, Sweden, lars.bjerkenstedt nvso.sll.se.

Efficacy and tolerability of Hypericum LI 160 was compared to fluoxetine and placebo in mild to moderate Major Depression (DSM-IV) in a 4-week randomized, double-blind trial. One hundred and sixtythree outpatients from 15 general practitioner centers received either 900 mg Hypericum LI 160, 20 mg fluoxetine, or placebo daily. Amelioration was measured by the Hamilton and the Montgomery-Asberg Depression scales. Response and remission rates and global ratings by investigators and patients were measured. Adverse event reports, laboratory screening, vital signs, physical exams and ECG were collected. No significant differences could be observed regarding efficacy measures except for remission rate (Hypericum 24%; fluoxetine 28%; placebo 7 %). Hypericum was significantly better tolerated than fluoxetine. Hypericum LI 160 or fluoxetine were not more effective in short-term treatment in mild to moderate depression than placebo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15538592&dopt=Abstract fluoxetine Prozac