Research and Clinical Trials on Paroxetine (Paxil, Seroxat, Deroxat)

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This list of current clinical research trials on Paroxetine (Paxil, Seroxat, Deroxat) is followed by a short set of abstracts from the most recent research articles published on the drug.

Paroxetine (Paxil, Seroxat, Deroxat) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Paroxetine (Paxil, Seroxat, Deroxat).

 

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Current Research Literature on Paroxetine (Paxil, Seroxat, Deroxat)

Here are abstracts for some of the latest research articles to have appeared on Paroxetine (Paxil, Seroxat, Deroxat):

A modified single-prolonged stress model for post-traumatic stress disorder.

Neurosci Lett. 2008 Jun 18;
Wen W, Yu L, Hong Z, Huaning W, Xiang J, Yunchun C, Lina Z, Xiaoxing L, Qingrong T
In the rat, single-prolonged stress (SPS) model produces a core symptom of post-traumatic stress disorder (PTSD), the enhanced fear response to the traumatic cue (conditioned fear response). This investigative tool is typically used for PTSD studies. However, whether SPS can produce another core symptom of PTSD, hyperarousal (the sensitized fear response in animal models), has not been evaluated. It is also not clear whether SPS can enhance both conditioned and sensitized fear responses after different incubation times. In this study, a single inescapable electric foot shock was given to rats immediately after SPS procedures (SPS&S). After different incubation times (1, 7 or 14 days), the conditioned or sensitized fear response was measured by re-exposing the stressed rats to the shock context or a neutral tone in a novel environment. Additionally, paroxetine, a selective serotonin reuptake inhibitor (SSRI) was administered after SPS&S for 14 days to test its potential preventive effect on PTSD-like symptoms. We observed that conditioned fear persisted and sensitized fear increased with ongoing incubation times after SPS&S. Early rapid intervention with paroxetine after SPS&S ameliorated PTSD-like symptoms in both fear responses and anxiety behaviors. Our data suggests that this modified SPS&S model may be both novel and predictably mimic the clinical characteristics of PTSD better than other investigative paradigms.

Binding of Paroxetine to the Serotonin Transporter in Membranes from Different Cells, Subcellular Fractions and Species.

Neurochem Res. 2008 Jun 18;
Cupello A, Albano C, Gatta E, Scarrone S, Villa E, Zona G
The binding of [(3)H]-paroxetine to membrane serotonin transporter (SERT) has been studied in membranes from different sources and subcellular fractions. From rat were membranes from venous blood platelets, brain total cortex, brain microsomes, brain crude and purified synaptosomes. Membranes were obtained from venous blood platelets from human volunteers and from brain cortex tissue from neurosurgery (cerebral lobectomies following craniocerebral injuries). The main finding was that the K (D) of paroxetine binding to the SERT was the same for platelet and nerve ending (synaptosomal) membranes. That parameter was significantly lower in membranes from brain microsomes and cortex total tissue. No species related difference was found, where comparison was possible, between human and rat tissue. The equality of K (D) of paroxetine binding to blood platelet membranes and to membranes from nerve endings appears to encourage the use of such membranes as a model for brain SERT. Binding at two different temperatures for several of the fractions suggests that paroxetine-SERT interaction is entropy-driven.

Management Strategies for Premenstrual Syndrome/Premenstrual Dysphoric Disorder (July/August) (CE).

Ann Pharmacother. 2008 Jun 17;
Jarvis CI, Lynch AM, Morin AK
OBJECTIVE: To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). DATA SOURCES: Literature was obtained through searches of MEDLINE Ovid (1950-March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. STUDY SELECTION AND DATA EXTRACTION: All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. DATA SYNTHESIS: Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. CONCLUSIONS: Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on individual patient symptoms, concomitant medical history, and need for contraception.

Determination of Basic Antidepressants and Their N-Desmethyl Metabolites in Raw Sewage and Wastewater Using Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

Anal Chem. 2008 Jun 14;
Lajeunesse A, Gagnon C, Sauvé S
A novel analytical method has been developed for the determination of six basic antidepressants (venlafaxine, sertraline, paroxetine, citalopram, amitriptyline, and fluoxetine) and four of their metabolites ( O-desmethylvenlafaxine, desmethylsertraline, nortriptyline, and norfluoxetine) in raw sewage and roughly primary-treated wastewater. For analytical development purposes, two ion exchange solid-phase extraction cartridges were compared. Extracts were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray (+ESI) and selected reaction monitoring transitions. The choice of a basic mobile phase significantly improved the instrumental sensitivity (by up to 14-fold for norfluoxetine) relative to common +ESI acidic mobile phases. In addition to the remarkable gain in sensitivity, negligible matrix effects were also observed in the raw sewage samples. Analyte recoveries ranged from 80 to 103% and effluent detection limits from 0.048 to 0.10 ng/L. Samples collected at the Montreal Wastewater Treatment Plant showed the unequivocal presence of all the target compounds at concentrations of 2-346 ng/L. The target antidepressants were also detected in samples taken from the effluent receiving waters (i.e., the St. Lawrence River) but at lower concentrations (0.41-69 ng/L). The highly sensitive proposed method constitutes one of the best means for monitoring the environmental occurrence of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and some of their metabolites.

Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice.

Br J Pharmacol. 2008 Jun 16;
Kreilgaard M, Smith DG, Brennum LT, Sánchez C
Background and purpose:Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice.Experimental approach:Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [(3)H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([(3)H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response.Key results:The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL(-1), 18 ng mL(-1) and 24 ng mL(-1), respectively, with corresponding responses in the 5-HTP behavioral model being between 20-40% of the maximum.Conclusions and implications:Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6-21 ng mL(-1), 21-95 ng mL(-1) and 20-48 ng mL(-1) for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values.British Journal of Pharmacology advance online publication, 16 June 2008; doi:10.1038/bjp.2008.243.

 

This page was last reviewed by Dr Greg Mulhauser, Friday, 4 July 2008.

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