Home About us Contact
|
Home About us Contact | ||
|
|
||
Fluoxetine
Terms modified by Fluoxetine Selected AbstractsKYNURENINE METABOLITES AND INFLAMMATION MARKERS IN DEPRESSED PATIENTS TREATED WITH FLUOXETINE OR COUNSELLINGCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009Gillian M Mackay SUMMARY 1Depression could result from changes in tryptophan availability caused by activation of the kynurenine pathway as a result of inflammation. In the present study, we examined patients newly diagnosed with depression to determine whether kynurenines and related factors change in parallel with improvements in mood. 2Concentrations of 5-hydroxytryptamine (5-HT; serotonin), 5-hydroxyindoleacetic acid (5-HIAA), oxidized tryptophan metabolites, brain-derived neurotrophic factor (BDNF) and inflammatory mediators (interleukin (IL)-2, C-reactive protein (CRP), neopterin) were measured in peripheral blood during an 18 week period of treatment with fluoxetine, fluoxetine plus tri-iodothyronine (T3) or psychiatric counselling. 3The results showed significant improvements in mood, with reduced 5-HT concentrations in patients given fluoxetine and a rise in plasma tryptophan in patients given counselling or fluoxetine and T3. The addition of T3 to the fluoxetine regimen appeared to slow recovery from depression, although the use of T3 was associated with a fall in thyroxine concentrations. Changes in 5-HT concentrations did not correlate with psychiatric scores and were seen only in drug-treated groups, not those given counselling. There were no associated changes in absolute concentrations of kynurenines, BDNF, CRP, neopterin or IL-2. With fluoxetine treatment, there were correlations between the concentrations of kynurenine metabolites and the psychiatric rating scores, whereas no correlations were found with BDNF or inflammatory markers. 4It is concluded that depression scores are largely independent of inflammatory status, but kynurenine metabolism may be related to the degree of depression after fluoxetine treatment. [source] Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptorsDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2007J. Parga Abstract Inductive signals mediating the differentiation of neural precursors into serotonergic (5-HT) or dopaminergic neurons have not been clarified. We have recently shown that in cell aggregates obtained from rat mesencephalic precursors, reduction of serotonin levels induces a marked increase in generation of dopaminergic neurons. In the present study we treated rat neurospheres with antagonists of the main subtypes of 5-HT receptors, 5-HT transport inhibitors, or 5-HT receptor agonists, and studied the effects on generation of dopaminergic neurons. Cultures treated with Methiothepin (5-HT1,2,5,6,7 receptor antagonist), the 5-HT4 receptor antagonist GR113808;67:00,.or the 5-HT7 receptor antagonist SB 269970 showed a significant increase in generation of dopaminergic cells. Treatment with the 5-HT1B/1D antagonist GR 127935, the 5-HT2 antagonist Ritanserin, the 5-HT transporter inhibitor Fluoxetine, the dopamine and norepinephrine transport inhibitor GBR 12935, or with both inhibitors together, or 5-HT4 or 5-HT7 receptor agonists induced significant decreases in generation of dopaminergic cells. Cultures treated with WAY100635 (5-HT1A receptor antagonist), the 5-HT3 receptor antagonist Ondasetron, or the 5-HT6 receptor antagonist SB 258585 did not show any significant changes. Therefore, 5-HT4 and 5-HT7 receptors are involved in the observed serotonin-induced decrease in generation of dopaminergic neurons from proliferating neurospheres of mesencephalic precursors. 5-HT4 and 5-HT7 receptors were found in astrocytes and serotonergic cells using double immunolabeling and laser confocal microscopy, and the glial receptors appeared to play a major role. © 2006 Wiley Periodicals, Inc. J Neurobiol 67: 10,22, 2007 [source] Laboratory persistence and fate of fluoxetine in aquatic environmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2006Jeong-Wook Kwon Abstract The persistence and fate of fluoxetine, a selective serotonin reuptake inhibitor, has been investigated in laboratory-scale experiments, including studies with various aqueous solutions, water/sediment systems, and activated sludge-amended medium. The samples were placed in the dark and/or in a growth chamber fitted with fluorescent lamps simulating the ultraviolet output of sunlight. Over a period of 30 d, fluoxetine was hydrolytically and photolytically stable in all aqueous solutions except synthetic humic water (pH 7), in which the degradation rate was increased by approximately 13-fold in comparison with buffered solutions at the same pH. Fluoxetine rapidly dissipated from the aqueous phase in water/sediment systems, primarily because of distribution to sediments. The dissipation rate from the aqueous phase was similar between light and dark systems, indicating a low contribution of photodegradation to the dissipation of fluoxetine in this system. The potential impact of fluoxetine in aquatic environments would be decreased because of adsorption to sediments. Based on results of ready-biodegradability investigations, fluoxetine would not be expected to rapidly biodegrade in wastewater treatment plants. A photoproduct was detected only in a sample of synthetic humic water and was identified as norfluoxetine formed by demethylation. Results indicate that fluoxetine is relatively recalcitrant to hydrolysis, photolysis, and microbial degradation and that it is rapidly removed from surface waters by adsorption to sediment, where it appears to be persistent. [source] Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2005Helen E. Grote Abstract Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice. [source] Metabolic drug interactions with new psychotropic agentsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Edoardo Spina Abstract New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and ,third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s). [source] Skeletal Fluorosis From Instant Tea,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008Michael P Whyte MD Abstract Introduction: Skeletal fluorosis (SF) can result from prolonged consumption of well water with >4 ppm fluoride ion (F,; i.e., >4 mg/liter). Black and green teas can contain significant amounts of F,. In 2005, SF caused by drinking 1,2 gallons of double-strength instant tea daily throughout adult life was reported in a 52-yr-old woman. Materials and Methods: A 49-yr-old woman developed widespread musculoskeletal pains, considered fibromyalgia, in her mid-30s. Additionally, she had unexplained, increasing, axial osteosclerosis. She reported drinking 2 gallons of instant tea each day since 12 yr of age. Fluoxetine had been taken intermittently for 5 yr. Ion-selective electrode methodology quantitated F, in her blood, urine, fingernail and toenail clippings, tap water, and beverage. Results: Radiographs showed marked uniform osteosclerosis involving the axial skeleton without calcification of the paraspinal, intraspinal, sacrotuberous, or iliolumbar ligaments. Minimal bone excrescences affected ligamentous attachments in her forearms and tibias. DXA Z-scores were +10.3 in the lumbar spine and +2.8 in the total hip. Her serum F, level was 120 ,g/liter (reference range, 20,80 ,g/liter), and a 24-h urine collection contained 18 mg F,/g creatinine (reference value, <3). Fingernail and toenail clippings showed 3.50 and 5.58 mg F,/kg (control means, 1.61 and 2.02, respectively; ps < 0.001). The instant tea beverage, prepared as usual extra strength using tap water with ,1.2 ppm F,, contained 5.8 ppm F,. Therefore, the tea powder contributed ,35 mg of the 44 mg daily F, exposure from her beverage. Fluoxetine provided at most 3.3 mg of F, daily. Conclusions: SF from habitual consumption of large volumes of extra strength instant tea calls for recognition and better understanding of a skeletal safety limit for this modern preparation of the world's most popular beverage. [source] Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative responseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006Thomas S. Breza Jr Introduction:, Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. Materials and Methods:, Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. Results:, An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. Conclusion:, Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation. [source] Chinese medicine Banxia-houpu decoction regulates c-fos expression in the brain regions in chronic mild stress model in ratsPHYTOTHERAPY RESEARCH, Issue 3 2004Weiyun Zhang Abstract Banxia-houpu decoction is a safe and effective traditional Chinese medicinal formula used in the treatment of mild and manic-depressive disorders for centuries. There has been increasing interest in its therapeutic application in depression. However, the mechanisms behind behavioural changes are still poorly understood. Chronic mild stress (CMS)-induced preference behaviour change has been used as a model to predict the clinical ef,cacy of many types of antidepressant treatment. Both EtOH and water extracts (AE and WE) of Banxia-houpu decoction exhibited a signi,cantly increased sucrose intake in the CMS model in rats, but there was no effect in unstressed animals. In the present study, it was found that the c-fos expression in cerebral cortex, hippocampus and striatum corpora were very high in the CMS model in rats. WE and AE at a dose of 130 mg/kg exhibited a signi,cantly decreased c-fos expression in the cerebral regions in CMS model in rats, respectively. The former was more potent than the latter. However, no signi,cant changes in the c-fos expression were observed in unstressed rats treated with the decoction. Fluoxetine not only signi,cantly reduced c-fos expression in all regions in the CMS model in rats, but only showed a marked decrease in c-fos expression in the hippocampus in unstressed animals. A different molecular mechanism of Banxia-houpu decoction and ,uoxetine may be implied. The cerebral cortex, hippocampus and striatum conpora might be important structural substrates in the central nervous system mediating the section of the Banxia-houpu decoction on preference behaviour in CMS-induced rats, and fos protein might be the common substrate of the signal transduction process of the decoction. Copyright © 2004 John Wiley & Sons, Ltd. [source] Study of the Efficacy of Fluoxetine and Clomipramine in the Treatment of Premature Ejaculation after Opioid DetoxificationTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2006Ebrahim Abdollahian MD Premature ejaculation is a common symptom that can provoke relapse in formerly opioid-dependent men after detoxification. The purpose of this study was to compare the efficacy of clomipramine and fluoxetine for the treatment of premature ejaculation in formerly opioid-dependent men after detoxification. Sixty opium-detoxified men with A & B DSM,IV diagnostic criteria for premature ejaculation participated in a prospective two-week descriptive inferential clinical trial after a two-week washout period. The subjects did not consume any other medications but naltrexone for maintenance of an opium-free state. The subjects were randomly divided into two groups of thirty subjects, one group received fluoxetine (10 mg/d for the first and 20 mg/d for the second week), and the other received clomipramine (25 mg/d for the first and 50mg/d for the second week). Twenty five subjects did not continue the treatment and were lost to follow-up. The severity of the premature ejaculation was graded regarding the subjects' report in weeks 0, 1, and 2. Mann Whitney-U and Wilcoxon non-parametric tests were used for statistical analysis. Fluoxetine (10 mg/d then 20 mg/d) and clomipramine (25 mg/d then 50mg/d) were both effective in the treatment of premature ejaculation and did not show any difference in efficacy. The severity of premature ejaculation did not show any relation to the subjects' age, education level, opioid type, or route of abuse. Fluoxetine and clomipramine both can be equally used in the treatment of premature ejaculation following opioid detoxification, depending on their side effects and other symptoms in the subjects. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Fluoxetine-Induced Decrements in Sexual Responses of Female Rats and Hamsters Are Reversed by 3,,5,-THPTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Cheryl A. Frye PhD ABSTRACT Introduction., Sexual dysfunction, as a result of selective-serotonin reuptake inhibitor (SSRI) treatment among women, is relatively common and is a factor in medication compliance. The mechanisms that underlie these side-effects of SSRIs are not well-understood. SSRIs can alter activity of catabolic enzymes that are involved in progesterone's conversion to 5,-pregnan-3,-ol-20-one (3,,5,-THP). 3,,5,-THP plays a key role in female reproductive physiology and behavior. Aims., This study aimed to determine whether 3,,5,-THP, in the midbrain ventral tegmental area (VTA) may be a potential mechanism for fluoxetine's reduction in sexual responding of female rodents. We hypothesized that if fluoxetine induces decrements in sexual responding in part through actions of 3,,5,-THP, then fluoxetine will inhibit sexual receptivity concomitant with reducing 3,,5,-THP levels, effects which can be reversed by 3,,5,-THP administration. Methods., Experiment 1 investigated effects of acute systemic fluoxetine [20 mg/kg intraperitoneal (IP)] and/or 3,,5,-THP [500 µg, subcutaneous (SC)] administration on sexual responding of ovariectomized, hormone-primed rats. Experiment 2 examined effects of 3,,5,-THP administration to the midbrain VTA (100 ng) on fluoxetine-induced decrements in lordosis of ovariectomized, hormone-primed rats and hamsters. Main Outcome Measures., Sexual responding was determined in rats and hamsters. For rats, the percentage of times that the lordosis response occurred following mounting by a sexually-vigorous male (lordosis quotients) was utilized. For hamsters, lateral displacement, the pelvic movement that females will make to facilitate intromissions by a male hamster, was utilized. Results., Fluoxetine significantly reduced lordosis, and this was reversed SC 3,,5,-THP. Intra-VTA 3,,5,-THP attenuated fluoxetine's detrimental effects on lordosis quotients and lateral displacement of rats and hamsters, respectively. Conclusions., Thus, fluoxetine's effects to disrupt female sexual responses may involve its effects on progestogens in the midbrain VTA. Frye CA, and Rhodes ME. Fluoxetine-induced decrements in sexual responses of female rats and hamsters are reversed by 3,,5,-THP. J Sex Med 2010;7:2670,2680. [source] Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptorsARTHRITIS & RHEUMATISM, Issue 3 2010Sandra Sacre Objective Selective serotonin reuptake inhibitors (SSRIs), in addition to their antidepressant effects, have been reported to have antiinflammatory effects. The aim of this study was to assess the antiarthritic potential of 2 SSRIs, fluoxetine and citalopram, in murine collagen-induced arthritis (CIA) and in a human ex vivo disease model of rheumatoid arthritis (RA). Methods Following therapeutic administration of SSRIs, paw swelling was assessed and clinical scores were determined daily in DBA/1 mice with CIA. Joint architecture was examined histologically at the end of the treatment period. Cultures of human RA synovial membranes were treated with SSRIs, and cytokine production was measured. Toll-like receptor (TLR) function was examined in murine and human macrophages, human B cells, and human fibroblast-like synovial cells treated with SSRIs. Results Both SSRIs significantly inhibited disease progression in mice with CIA, with fluoxetine showing the greatest degree of efficacy at the clinical and histologic levels. In addition, both drugs significantly inhibited the spontaneous production of tumor necrosis factor, interleukin-6, and interferon-,,inducible protein 10 in human RA synovial membrane cultures. Fluoxetine and citalopram treatment also inhibited the signaling of TLRs 3, 7, 8, and 9, providing a potential mechanism for their antiinflammatory action. Conclusion Fluoxetine and citalopram treatment selectively inhibit endosomal TLR signaling, ameliorate disease in CIA, and suppress inflammatory cytokine production in human RA tissue. These data highlight the antiarthritic potential of the SSRI drug family and provide further evidence of the involvement of TLRs in the pathogenesis of RA. The SSRIs may provide a template for potential antiarthritic drug development. [source] Effects of repeated maprotiline and fluoxetine treatment on gene expression of catecholamine synthesizing enzymes in adrenal medulla of unstressed and stressed ratsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2010N. Spasojevic Summary 1,Repeated maprotiline (a noradrenaline reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor) treatment on gene expression of catecholamine biosynthetic enzymes were examined in adrenal medulla of unstressed control and chronic unpredictable mild stressed rats. 2,Maprotiline did not change gene expression of catecholamine biosynthetic enzymes in control and stressed rats. 3,Fluoxetine increased gene expression of tyrosine hydroxylase (TH) and dopamine-,-hydroxylase (DBH), but did not phenylethanolamine N -methyltransferase in both unstressed and chronic unpredictable mild stressed animals. 4,In conclusion, we have demonstrated that repeated administration of fluoxetine enhanced gene transcription of TH and DBH and subsequently stimulates noradrenaline synthesis in adrenal medulla of control and stressed rats. [source] Goldenhar syndrome associated with prenatal maternal Fluoxetine ingestion: Cause or coincidence?BIRTH DEFECTS RESEARCH, Issue 7 2010Chantal Farra Abstract Goldenhar syndrome, also known as oculo-auriculo-vertebral spectrum, is a complex, heterogeneous condition characterized by abnormal prenatal development of facial structures. We present the occurrence of Goldenhar syndrome in an infant born to a woman with a history of prenatal Fluoxetine ingestion throughout her pregnancy. Because this is the first reported case associating maternal Fluoxetine intake with fetal craniofacial malformations, a potential mechanism of injury is discussed. The propositus, a male born from nonconsanguinous parents, had facial asymmetry with right microtia and mandibular hypoplasia; he also had bilateral hypoplastic macula, scoliotic deformity of the thoracic spine, and ventricular septal defect. The mother was under treatment with Fluoxetine 20 mg/day prior to conception and maintained the same dosage throughout her pregnancy. The drug is a selective serotonin re-uptake inhibitor, the most widely prescribed for the treatment of depression. The occurrence of developmental aberrations may be caused by a profound serotonin receptor suppressive state in utero leading to aberrant clinical manifestations of the first and second branchial arches. Despite the very many limitations of case reporting of teratogenic events, it remains an important source of information on which more advanced research is based. Birth Defects Research (Part A) 2010. © 2010 Wiley-Liss, Inc. [source] Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placentaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 9 2002Tuija Heikkinen Objective To investigate the transplacental transfer and the effects of protein binding on the transfer of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine in the isolated perfused human placenta model. Design Prospective observational study. Methods Fifteen term human placentas were obtained immediately after delivery with maternal consent and a 2-hour non-recirculating perfusion cycle of a single placental cotyledon was set up. Citalopram (1230 nmol/L) and desmethylcitalopram (600 nmol/L) or fluoxetine (1455 nmol/L) and desmethylfluoxetine (1525 nmol/L) were added to the maternal reservoir and their appearance to the fetal circulation was followed by repeated measurements. To investigate the effect of protein binding on the transfer of citalopram and fluoxetine, nine additional perfusions were performed without albumin in the perfusion medium. Citalopram and desmethylcitalopram concentrations were measured by reversed-phase high performance liquid chromatography. Fluoxetine and desmethylfluoxetine concentrations was measured by gas chromatography and antipyrine (used as a reference compound) concentrations spectrophotometrically. Results The mean (SD) steady-state transplacental transfer (TPTSS%) for citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine was 9.1%, 5.6% (P= 0.017 compared with citalopram), 8.7% and 9.1%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPTSS%s of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine were 86%, 50%, 88% and 91% of that of freely diffusable antipyrine. The absence of albumin significantly reduced the transfer of citalopram and fluoxetine (TPTSS% 1.1% and 4.8%, respectively) but not the transfer of antipyrine. Conclusion Citalopram, fluoxetine and desmethylfluoxetine all cross the human placenta, and may, therefore, affect the perinatal outcome of infants exposed to these drugs during pregnancy. The transfer of desmethylcitalopram was significantly lower, which in the clinical setting may suggest lower fetal exposure of serotonin re-uptake inhibition by citalopram compared with fluoxetine. The presence of albumin was necessary for the transplacental transfer of both citalopram and fluoxetine. [source] Effect of serotonin-acting agents on the serotonin content of immune cells.CELL BIOCHEMISTRY AND FUNCTION, Issue 5 2007A peculiar observation Abstract The effect of the tryptophan hydroxylase inhibitor, PCPA methylester, the serotonin reuptake inhibitor fluoxetine and MAO-A inhibitor clorgyline on the serotonin content of rat immune cells was studied, using labelled antibodies and flow cytometry. Each molecule significantly increased in males the serotonin concentration of peritoneal lymphocytes and the monocyte-macrophage-granulocyte group (mo-gran), however the agents were ineffective towards mast cells. In females fluoxetine and clorgyline increased the serotonin concentration in peritoneal lymphocytes and mo-gran. Fluoxetine also increased the serotonin level in mast cells. Thymus was absolutely resistant to the drugs in both genders. The results call attention (1) to the reverse effect of serotonin-acting agents on immune cells, (2) to the influence of the milieu where the cell is located and (3) the effect of gender. Copyright © 2006 John Wiley & Sons, Ltd. [source] Polymer-Supported Chiral Sulfonamide Catalyzed One-Pot Reduction of ,-Keto Nitriles: A Practical Synthesis of (R)-Fluoxetine and (R)-Duloxetine.CHEMINFORM, Issue 40 2005Guangyin Wang Abstract For Abstract see ChemInform Abstract in Full Text. [source] Does defense style or psychological mindedness predict treatement response in major depression?DEPRESSION AND ANXIETY, Issue 7 2009Kim Kronström M.D. Abstract Background: The aim of this study was to define the impact of defense style and psychological mindedness (PM) on the prognosis of major depressive disorder (MDD) in patients treated with either fluoxetine (FLX) or short-term psychodynamic psychotherapy (STPP) in a randomized comparative study. Method: 50 patients with MDD received either STPP or FLX treatment for 16 weeks. The Hamilton Depression Rating Scale (HDRS) was the outcome measure completed at baseline and in the follow-ups at 4- and 12-months. Patients completed the Psychological Mindedness Scale (PMS) and the Defense Style Questionnaire at the baseline. Results: In the FLX group recovery measured by the decrease in the HDRS during the 4-month follow-up associated with baseline mature defense style (r=,.59, P=.015). There were no correlations between the PMS-scores and the outcome measures in either treatment groups nor defense status and the outcome in the STPP group. Conclusion: Mature defense style predicts good response to FLX therapy in major depression. This association was not found in the psychotherapy group. The results may imply that patients with immature defenses benefit relatively more from brief psychotherapy than medication. PM measured by the PMS was not useful in predicting recovery in MDD. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [source] Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptomsDEPRESSION AND ANXIETY, Issue 1 2002Jonathan R.T. Davidson M.D., M.B.A. Abstract Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces significantly higher remission rates in depressed patients than do the selective serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we explored the relationship between differences in treatment efficacy, early improvement of symptoms, and severity of baseline anxiety in depressed patients treated with either venlafaxine or fluoxetine. A pooled analysis was performed on data from 1,454 outpatients with major depression from five double-blind, randomized studies comparing the 6-week efficacy of venlafaxine (542 patients) with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D) total and item scores were analyzed at different treatment times up to 6 weeks. Venlafaxine and fluoxetine both produced statistically significant higher response and remission rates compared with placebo starting from week 2 for response and weeks 3 to 4 for remission. Venlafaxine was statistically significantly superior to fluoxetine from week 3 until week 6 in respect of response rate, and from week 2 until week 6 for remission rate. After 1 week of treatment, greater improvement in individual symptoms was observed in the depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement in psychic anxiety was statistically significantly greater with venlafaxine than with fluoxetine. The presence of baseline psychic anxiety correlated significantly to treatment outcome when analyzing the remission rates. In depressed patients with moderate anxiety (HAM-D psychic anxiety score ,2), venlafaxine statistically significantly increased remission rates compared with placebo from week 4 until week 6, while a significant effect of fluoxetine on remission rates was observed starting at week 6. Remission rates in the severely anxious depressed patients (score >2) were statistically significantly higher with venlafaxine than placebo starting from week 3 until the end of the study period, but no difference could be observed between fluoxetine and placebo. Baseline severity of psychic anxiety had a significant impact on remission rates after treatment of patients diagnosed with depression. Venlafaxine's superior remission rates in the more severely anxious patients and its ability to improve psychic anxiety as early as week 1 compared with fluoxetine suggest that venlafaxine's early efficacy on anxiety symptoms may be the basis for its superior efficacy in depression. Depression and Anxiety 16:4,13, 2002. © 2002 Wiley-Liss, Inc. [source] Brain functional changes during placebo lead-in and changes in specific symptoms during pharmacotherapy for major depressionACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2009A. M. Hunter Objective:, Brain functional changes during placebo lead-in have been associated with antidepressant response in clinical trials for major depressive disorder (MDD); however, the relationship between such non-pharmacodynamic changes in brain function and changes in specific symptoms is unknown. Method:, Fifty-eight adults with MDD completed a 1-week single-blind placebo lead-in preceding 8 weeks of double-blind randomized treatment with fluoxetine or venlafaxine (n = 30) or placebo (n = 28). Brain functional change during lead-in was assessed using quantitative electroencephalographic (qEEG) prefrontal theta-band cordance. Symptoms were assessed using the Symptom Checklist-90-Revised (SCL-90-R). Results:, The multiple regression model examining the qEEG parameter in relation to SCL-90-R subscales was significant [F(9,9) = 4.27, P = 0.021, R2 = 0.81] in females, with a significant association for the interpersonal sensitivity subscale (beta coefficient = 1.94, P = 0.001). Conclusion:, Prefrontal neurophysiologic change during placebo lead-in may indicate subsequent antidepressant-related improvement in symptoms of interpersonal sensitivity. [source] On-line sample stacking and short-end injection CE for the determination of fluoxetine and norfluoxetine in plasma: Method development and validation using experimental designsELECTROPHORESIS, Issue 18 2007Chia-Chia Lu Abstract A short-end injection CE method combining field-amplified sample stacking (FASS) is presented for the analysis of fluoxetine (FL) and norfluoxetine in plasma. In this study, FASS enhanced the sensitivity about 1100-fold, while short-end injection reduced the analysis time to less than 4,min. Parameters involved in the separations were investigated using a central composite design (CCD) and response surface methodology to optimize the separation conditions in a total of only 32 runs. Samples injected into the capillary for 99.9,s at a voltage of ,5,kV were stacked in a water plug (0.5,psi, 9,s). Baseline resolution of FL and its major metabolite was achieved using a BGE formulation consisting of phosphate,triethanolamine at low pH, and a separation voltage of ,10,kV. Five percent methanol was added as organic modifier to enhance selectivity and resolution. The linear range was between 10 and 500,ng/mL (r >0.9946), covering the expected plasma therapeutic ranges. The LOD in plasma were 4,ng/mL (S/N,=,3), a value comparable to that obtained using LC-MS, showing the success of the on-line stacking technique. Our method was also successfully validated in quantification and pharmacokinetic studies with three volunteer plasma samples and could be applied to pharmacogenetic studies. [source] Advances in the enantioseparation of second-generation antidepressant drugs by electrodriven methodsELECTROPHORESIS, Issue 1 2006Roberto Mandrioli Abstract Stereochemistry is steadily increasing in importance in the development of new drugs, and the availability of pure enantiomer drugs can make therapy safer and more efficacious. In particular, almost all second-generation antidepressant drugs possess one or more chiral centres; however, only some of them are administered as single enantiomers. A fundamental part of the quality control of pharmaceutical formulations is the determination of enantiomeric excess and enantiomeric purity; this is also important for the therapeutic drug monitoring of depressed patients. For this purpose, efficient and reliable analytical methods are needed and electrodriven techniques (most of all CE, CEC and MEKC) are very efficient and inexpensive candidates for the role. In this review, the enantioselective electrodriven methods available for the analysis of second-generation antidepressant are presented and discussed. In particular, the following pharmacological classes of antidepressants will be considered: selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine, sertraline); norepinephrine reuptake inhibitors (reboxetine); serotonin and norepinephrine reuptake inhibitors (venlafaxine, milnacipran, duloxetine); and noradrenergic and specific serotonergic antidepressants (mirtazapine). [source] Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershedENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010Chris D. Metcalfe Abstract Antidepressants are a widely prescribed group of pharmaceuticals that can be biotransformed in humans to biologically active metabolites. In the present study, the distribution of six antidepressants (venlafaxine, bupropion, fluoxetine, sertraline, citalopram, and paroxetine) and five of their metabolites was determined in a municipal wastewater treatment plant (WWTP) and at sites downstream of two WWTPs in the Grand River watershed in southern Ontario, Canada. Fathead minnows (Pimephales promelas) caged in the Grand River downstream of a WWTP were also evaluated for accumulated antidepressants. Finally, drinking water was analyzed from a treatment plant that takes its water from the Grand River 17 km downstream of a WWTP. In municipal wastewater, the antidepressant compounds present in the highest concentrations (i.e., >0.5 µg/L) were venlafaxine and its two demethylation products, O - and N -desmethyl venlafaxine. Removal rates of the target analytes in a WWTP were approximately 40%. These compounds persisted in river water samples collected at sites up to several kilometers downstream of discharges from WWTPs. Venlafaxine, citalopram, and sertraline, and demethylated metabolites were detected in fathead minnows caged 10 m below the discharge from a WWTP, but concentrations were all <7 µg/kg wet weight. Venlafaxine and bupropion were detected at very low (<0.005 µg/L) concentrations in untreated drinking water, but these compounds were not detected in treated drinking water. The present study illustrates that data are needed on the distribution in the aquatic environment of both the parent compound and the biologically active metabolites of pharmaceuticals. Environ. Toxicol. Chem. 2010;29:79,89. © 2009 SETAC [source] Factors affecting the degradation of pharmaceuticals in agricultural soils,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Sara C. Monteiro Abstract Pharmaceuticals may be released to the soil environment through the application of biosolids to land. To understand those factors affecting the persistence of pharmaceuticals in the soil environment, the present study was performed to assess the effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d and in biosolids with a half-life of 10.2 d. No relationships were observed between degradation rate and soil physicochemical properties and soil bioactivity. For naproxen, addition of biosolids to soils reduced the degradation rate observed in the soil-only studies, with half-lives in the soil-biosolid systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was assessed using a mixture of the three study compounds and the sulfonamide antibiotic sulfamethazine, the degradation behavior of fluoxetine and carbamazepine was similar to that observed in the single compound studies (i.e., no degradation). However, the degradation rate of naproxen in soils, biosolids, and soil-biosolid systems spiked with the mixture was significantly slower than in the single-compound studies. As degradation studies for risk assessment purposes are performed using single substances in soil-only studies, it is possible that current risk assessment procedures will underestimate environmental impacts. Further work is therefore warranted on a larger range of substances, soils, biosolid types, and chemical mixtures to better understand the fate of pharmaceuticals in terrestrial systems. [source] Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceansENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Anne Munch Christensen Abstract Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications, primarily in the treatment of clinical depression. They are among the pharmaceuticals most often prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqueous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) as single substances and of citalopram, fluoxetine, and sertraline in binary mixtures in two standardized bioassays. Test organisms were the freshwater algae Pseudokirchneriella subcapitata and the freshwater crustacean Daphnia magna. In algae, test median effect concentrations (EC50s) ranged from 0.027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two bioassays is predictable by the model of concentration addition. Therefore, in risk assessment based on chemical analysis of environmental samples, it is important to include the effect of all SSRIs that are present at low concentrations, and the model of concentration addition may be used to predict the combined effect of the mixture of SSRIs. [source] Laboratory persistence and fate of fluoxetine in aquatic environmentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2006Jeong-Wook Kwon Abstract The persistence and fate of fluoxetine, a selective serotonin reuptake inhibitor, has been investigated in laboratory-scale experiments, including studies with various aqueous solutions, water/sediment systems, and activated sludge-amended medium. The samples were placed in the dark and/or in a growth chamber fitted with fluorescent lamps simulating the ultraviolet output of sunlight. Over a period of 30 d, fluoxetine was hydrolytically and photolytically stable in all aqueous solutions except synthetic humic water (pH 7), in which the degradation rate was increased by approximately 13-fold in comparison with buffered solutions at the same pH. Fluoxetine rapidly dissipated from the aqueous phase in water/sediment systems, primarily because of distribution to sediments. The dissipation rate from the aqueous phase was similar between light and dark systems, indicating a low contribution of photodegradation to the dissipation of fluoxetine in this system. The potential impact of fluoxetine in aquatic environments would be decreased because of adsorption to sediments. Based on results of ready-biodegradability investigations, fluoxetine would not be expected to rapidly biodegrade in wastewater treatment plants. A photoproduct was detected only in a sample of synthetic humic water and was identified as norfluoxetine formed by demethylation. Results indicate that fluoxetine is relatively recalcitrant to hydrolysis, photolysis, and microbial degradation and that it is rapidly removed from surface waters by adsorption to sediment, where it appears to be persistent. [source] Seasonality effects on pharmaceuticals and s -triazine herbicides in wastewater effluent and surface water from the Canadian side of the upper Detroit RiverENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2006Wen Yi Hua Abstract The influence of seasonal changes in water conditions and parameters on several major pharmacologically active compounds (PhACs) and s -triazine herbicides was assessed in the wastewater and sewage treatment plant (WSTP) effluent as well as the downstream surface water from sites on the Canadian side of the upper Detroit River, between the Little River WSTP and near the water intake of a major drinking water treatment facility for the City of Windsor (ON, Canada). The assessed PhACs were of neutral (carbamazepine, cotinine, caffeine, cyclophosphamide, fluoxetine, norfluoxetine, pentoxifylline, and trimethoprim) and acidic (ibuprofen, bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, indomethacin, naproxen, and ketoprofen) varieties. The major assessed s -triazine herbicides were atrazine, simazine, propazine, prometon, ametryn, prometryn, and terbutryn. At sampling times from September 2002 to June 2003, 15 PhACs were detected in the WSTP effluent at concentrations ranging from 1.7 to 1,244 ng/L. The PhAC concentrations decreased by as much 92 to 100% at the Little River/Detroit River confluence because of the river dilution effect, with further continual decreases at sites downstream from the WSTP. The only quantifiable s -triazine in WSTP effluent, atrazine, ranged from 6.7 to 200 ng/L and was higher in Detroit River surface waters than in WSTP effluent. Only carbamazepine, cotinine, and atrazine were detectable at the low-nanogram and subnanogram levels in surface waters near a drinking water intake site. Unlike the PhACs, atrazine in the Detroit River is not attributable to point sources, and it is heavily influenced by seasonal agricultural usage and runoff. Detroit River surface water concentrations of carbamazepine, cotinine, and atrazine may present a health concern to aquatic wildlife and to humans via the consumption of drinking water. [source] Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Chad A. Kinney Abstract Three sites in the Front Range of Colorado, USA, were monitored from May through September 2003 to assess the presence and distribution of pharmaceuticals in soil irrigated with reclaimed water derived from urban wastewater. Soil cores were collected monthly, and 19 pharmaceuticals, all of which were detected during the present study, were measured in 5-cm increments of the 30-cm cores. Samples of reclaimed water were analyzed three times during the study to assess the input of pharmaceuticals. Samples collected before the onset of irrigation in 2003 contained numerous pharmaceuticals, likely resulting from the previous year's irrigation. Several of the selected pharmaceuticals increased in total soil concentration at one or more of the sites. The four most commonly detected pharmaceuticals were erythromycin, carbamazepine, fluoxetine, and diphenhydramine. Typical concentrations of the individual pharmaceuticals observed were low (0.02,15 ,g/kg dry soil). The existence of subsurface maximum concentrations and detectable concentrations at the lowest sampled soil depth might indicate interactions of soil components with pharmaceuticals during leaching through the vadose zone. Nevertheless, the present study demonstrates that reclaimed-water irrigation results in soil pharmaceutical concentrations that vary through the irrigation season and that some compounds persist for months after irrigation. [source] Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubiaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2004Theodore B. Henry Abstract Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac®; fluvoxamine, Luvox®; paroxetine, Paxil®; citalopram, Celexa®; and sertraline, Zoloft®) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment. [source] Treatment emergent mania responding to valproate in a Chinese female adolescent population with eating disorders: A case seriesEUROPEAN EATING DISORDERS REVIEW, Issue 6 2008Phern Chern Tor Abstract Eating disorders are commonly associated with depressive symptoms. In an adolescent and binge eating population fluoxetine is commonly used to treat co-morbid depression associated with eating disorders. In some patients this may precipitate treatment emergent mania (TEM). Risk factors in the adolescent population include being older, female, having a longer duration of illness, more previous mood episodes, a higher prevalence of subclinical hypothyroidism, early-onset anxiety and recent exposure to a mood-elevating agent. Diagnosis and management of these co-morbid conditions is challenging due to the overlapping symptomatology and the adverse effects of both conditions complicating pharmacological management. This is illustrated with three cases in a Chinese female adolescent population that experienced TEM while on fluoxetine and responded to valproate. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association. [source] RESEARCH FOCUS ON COMPULSIVE BEHAVIOUR IN ANIMALS: Pre-exposure to environmental cues predictive of food availability elicits hypothalamic,pituitary,adrenal axis activation and increases operant responding for food in female ratsADDICTION BIOLOGY, Issue 4 2009Carlo Cifani ABSTRACT The present study was undertaken to develop an animal model exploiting food cue-induced increased motivation to obtain food under operant self-administration conditions. To demonstrate the predictive validity of the model, rimonabant, fluoxetine, sibutramine and topiramate, administered 1 hour before the experiment, were tested. For 5 days, female Wistar rats were trained to self-administer standard 45 mg food pellets in one daily session (30 minutes) under FR1 (fixed ratio 1) schedule of reinforcement. Rats were then trained to an FR3 schedule and finally divided into two groups. The first group (control) was subjected to a standard 30 minutes FR3 food self-administration session. The second group was exposed to five presentations of levers and light for 10 seconds each (every 3 minutes in 15 minutes total). At the completion of this pre-session phase, a normal 30-minute session (as in the control group) started. Results showed that pre-exposure to environmental stimuli associated to food deliveries increased response for food when the session started. Corticosterone and adrenocorticotropic hormone plasma levels, measured after the 15-minute pre-exposure, were also significantly increased. No changes were observed for the other measured hormones (growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, insulin, amylin, gastric inhibitor polypeptide, ghrelin, leptin, peptide YY and pancreatic polypeptide). Rimonabant, sibutramine and fluoxetine significantly reduced food intake in both animals pre-exposed and in those not pre-exposed to food-associated cues. Topiramate selectively reduced feeding only in pre-exposed rats. The present study describes the development of a new animal model to investigate cue-induced increased motivation to obtain food. This model shows face and predictive validity, thus, supporting its usefulness in the investigation of new potential treatments of binge-related eating disorders. In addition, the present findings confirm that topiramate may represent an important pharmacotherapeutic approach to binge-related eating. [source] | ||||||||||||||||||||||||||||||||||