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pharmacokinetics, antidepressant

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https://www.readbyqxmd.com/read/27900470/influence-of-the-selective-antagonist-of-the-nr2b-subunit-of-the-nmda-receptor-traxoprodil-on-the-antidepressant-like-activity-of-desipramine-paroxetine-milnacipran-and-bupropion-in-mice
#1
Weronika Stasiuk, Aleksandra Szopa, Anna Serefko, Elżbieta Wyska, Katarzyna Świąder, Jarosław Dudka, Piotr Wlaź, Ewa Poleszak
Pre-clinical and clinical studies indicated that a blockade of the NMDA receptor complex creates new opportunities for the treatment of affective disorders, including depression. The aim of the present study was to assess the influence of traxoprodil (10 mg/kg) on the activity of desipramine (10 mg/kg), paroxetine (0.5 mg/kg), milnacipran (1.25 mg/kg), and bupropion (10 mg/kg), each at sub-therapeutic doses. Moreover, brain levels of traxoprodil and tested agents were determined using HPLC. The obtained results were used to ascertain the nature of occurring interaction between traxoprodil and studied antidepressants...
November 29, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#2
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27888525/breaking-sad-unleashing-the-breakthrough-potential-of-ketamine-s-rapid-antidepressant-effects
#3
David Feifel
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h...
November 26, 2016: Drug Development Research
https://www.readbyqxmd.com/read/27854435/-rhodiola-rosea-and-its-neuropsychotropic-effects
#4
Jan Juřica, Tereza Koupá
The paper reviews the neuropsychotropic effects of Rhodiola rosea, a succulent perennial plant which is native to dry, high-altitude regions of the northern hemisphere. The most valued part of the plant is its rhizome, which has a rose-like fragrance. In the available literature, there is a large number of mentions of its healing properties; nonetheless, only few of them are based on reliable scientific evidence. Of the neuropsychotropic effects, there are mentions of anxiolytic, antidepressant, neuroprotective and pro- cognitive properties and nonspecific "adaptogenic" effects...
2016: Ceská a Slovenská Farmacie
https://www.readbyqxmd.com/read/27846049/agomelatine-for-the-treatment-of-major-depressive-episodes-in-schizophrenia-spectrum-disorders-an-open-prospective-proof-of-concept-study
#5
Susanne Englisch, Hanna Sophie Jung, Antje Lewien, Anna Becker, Ulrike Nowak, Hanna Braun, Jascha Thiem, Sarah Eisenacher, Andreas Meyer-Lindenberg, Mathias Zink
BACKGROUND: Depressive episodes in schizophrenia constitute a major clinical problem, and treatment success is often limited by treatment-emergent side effects. Agomelatine, an agonist at melatonergic MT1/MT2 receptors and 5-HT2C receptor antagonist, is a new antidepressant with a novel mode of action which constitutes a potential therapeutic option for depression in schizophrenia. METHODS: Twenty-seven patients with lifetime diagnoses within the schizophrenia spectrum and comorbid depression were treated with agomelatine in addition to stable doses of antipsychotic agents...
October 29, 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27836670/in-vitro-to-in-vivo-extrapolation-of-the-complex-drug-drug-interaction-of-bupropion-and-its-metabolites-with-cyp2d6-simultaneous-reversible-inhibition-and-cyp2d6-downregulation
#6
Jennifer E Sager, Sasmita Tripathy, Lauren S L Price, Abhinav Nath, Justine Chang, Alyssa Stephenson-Famy, Nina Isoherranen
Bupropion is a widely used antidepressant and smoking cessation aid and a strong inhibitor of CYP2D6 in vivo. Bupropion is administered as a racemic mixture of R- and S-bupropion and has stereoselective pharmacokinetics. Four primary metabolites of bupropion, threo- and erythro-hydrobupropion and R,R- and S,S-OH-bupropion, circulate at higher concentrations than the parent drug and are believed to contribute to the efficacy and side effects of bupropion as well as to the CYP2D6 inhibition. However, bupropion and its metabolites are only weak inhibitors of CYP2D6 in vitro, and the magnitude of the in vivo drug-drug interactions (DDI) caused by bupropion cannot be explained by the in vitro data even when CYP2D6 inhibition by the metabolites is accounted for...
November 9, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27816979/evaluation-of-the-potential-pharmacokinetic-interaction-between-atomoxetine-and-fluvoxamine-in-healthy-volunteers
#7
Ioana Todor, Adina Popa, Maria Neag, Dana Muntean, Corina Bocsan, Anca Buzoianu, Laurian Vlase, Ana-Maria Gheldiu, Corina Briciu
BACKGROUND/AIMS: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). METHODS: Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor...
November 5, 2016: Pharmacology
https://www.readbyqxmd.com/read/27805978/agomelatine-for-the-treatment-of-major-depressive-episodes-in-schizophrenia-spectrum-disorders-an-open-prospective-proof-of-concept-study
#8
Susanne Englisch, Hanna Sophie Jung, Antje Lewien, Anna Becker, Ulrike Nowak, Hanna Braun, Jascha Thiem, Sarah Eisenacher, Andreas Meyer-Lindenberg, Mathias Zink
BACKGROUND: Depressive episodes in schizophrenia constitute a major clinical problem, and treatment success is often limited by treatment-emergent side effects. Agomelatine, an agonist at melatonergic MT1/MT2 receptors and 5-HT2C receptor antagonist, is a new antidepressant with a novel mode of action which constitutes a potential therapeutic option for depression in schizophrenia. METHODS: Twenty-seven patients with lifetime diagnoses within the schizophrenia spectrum and comorbid depression were treated with agomelatine in addition to stable doses of antipsychotic agents...
December 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27803666/inhibitors-of-mao-a-and-mao-b-in-psychiatry-and-neurology
#9
REVIEW
John P M Finberg, Jose M Rabey
Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines ("cheese effect")...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27771379/novel-highly-potent-and-in%C3%A2-vivo-active-inhibitor-of-gaba-transporter-subtype-1-with-anticonvulsant-anxiolytic-antidepressant-and-antinociceptive-properties
#10
Kinga Sałat, Adrian Podkowa, Natalia Malikowska, Felix Kern, Jörg Pabel, Ewelina Wojcieszak, Katarzyna Kulig, Klaus T Wanner, Beata Strach, Elżbieta Wyska
BACKGROUND AND PURPOSE: Since GABAergic dysfunction underlies a variety of neurological and psychiatric disorders, numerous strategies leading to the augmentation of GABAergic neurotransmission have been introduced. One of them is the inhibition of GABA reuptake from the synaptic cleft mediated by four plasma membrane GABA transporters (GAT1-4). GAT1 which is exclusively expressed in the brain is an interesting target for centrally acting drugs. In this research, pharmacological properties of a novel, highly potent and selective inhibitor of GAT1, the guvacine derivative named DDPM-2571, were assessed in vivo...
October 19, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27751669/review-of-safety-and-efficacy-of-sleep-medicines-in-older-adults
#11
REVIEW
Jennifer L Schroeck, James Ford, Erin L Conway, Kari E Kurtzhalts, Megan E Gee, Krista A Vollmer, Kari A Mergenhagen
PURPOSE: Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are used. The pharmacokinetics of agents used to treat insomnia may be altered. This review focuses on the safety and efficacy of medications used to treat insomnia. METHODS: A literature search of Medline, PubMed, and Embase was conducted (January 1966-June 2016). It included systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on insomnia in an older population...
November 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27631529/-update-palliative-pain-therapy
#12
R Rolke, S Rolke, S Hiddemann, M Mücke, H Cuhls, L Radbruch, F Elsner, V Peuckmann-Post
Cancer pain and pain associated with non-neoplastic diseases can be associated with pain mechanisms, such as a peripheral or central sensitization or deafferentation. The clarification allows indirect conclusions about the underlying mechanisms based on clinical signs, such as allodynia or hyperalgesia. Non-opioid analgesics are the basis of cancer pain therapy according to the World Health Organization (WHO) pain ladder. In the case of severe cancer pain, treatment can be escalated directly from level 1 to level 3...
October 2016: Der Internist
https://www.readbyqxmd.com/read/27578365/ketamine-dependent-neuronal-activation-in-healthy-volunteers
#13
Anna Höflich, Andreas Hahn, Martin Küblböck, Georg S Kranz, Thomas Vanicek, Sebastian Ganger, Marie Spies, Christian Windischberger, Siegfried Kasper, Dietmar Winkler, Rupert Lanzenberger
Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S(®)) was administered intravenously to 35 healthy volunteers...
August 30, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27557550/regional-differences-in-serotonin-transporter-occupancy-by-escitalopram-an-11-c-dasb-pk-pd-study
#14
Euitae Kim, Oliver D Howes, Bo-Hyung Kim, Myong-Wuk Chon, Seongho Seo, Federico E Turkheimer, Jae Sung Lee, Yun-Sang Lee, Jun Soo Kwon
BACKGROUND AND OBJECTIVE: Escitalopram is one of the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs). It is thought to act by blocking the serotonin transporter (SERT). However, its dose-SERT occupancy relationship is not well known, so it is not clear what level of SERT blockade is achieved by currently approved doses. METHODS: To determine the dose-occupancy relationship, we measured serial SERT occupancy using [(11)C]DASB [3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] positron emission tomography (PET) and plasma drug concentrations after the administration of escitalopram in 12 healthy volunteers...
August 24, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27551817/progressing-preemptive-genotyping-of-cyp2c19-allelic-variants-for-sickle-cell-disease-patients
#15
Cheedy Jaja, Nadine Barrett, Niren Patel, Matt Lyon, Hongyan Xu, Abdullah Kutlar
AIMS: Interindividual variability in drug response and adverse effects have been described for proton pump inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, tricyclic antidepressants, and anti-infectives, but little is known about the safety and efficacy of these medications in patients with sickle cell disease (SCD). We genotyped the CYP2C19 gene which has been implicated in the metabolism of these drugs in an SCD patient cohort to determine the frequencies of reduced function, increased function, or complete loss-of-function variants...
October 2016: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/27495292/stereoselective-metabolism-of-bupropion-to-oh-bupropion-threohydrobupropion-erythrohydrobupropion-and-4-oh-bupropion-in-vitro
#16
Jennifer E Sager, Lauren S L Price, Nina Isoherranen
Bupropion is a widely used antidepressant, smoking cessation aid, and weight-loss therapy. It is administered as a racemic mixture, but the pharmacokinetics and activity of bupropion are stereoselective. The activity and side effects of bupropion are attributed to bupropion and its metabolites S,S- and R,R-OH-bupropion, threohydrobupropion, and erythrohydrobupropion. Yet the stereoselective metabolism in vitro and the enzymes contributing to the stereoselective disposition of bupropion have not been characterized...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27467032/-pharmacokinetic-and-pharmacodynamic-effects-of-psychotropic-medications-differences-between-sexes
#17
J D Bergiannaki, P Kostaras
The gender based or gender sensitive pharmacology is a new research area. Differences among sexes are observed in several parameters of their pharmacokinetic which may relate to alteration of their pharmacodynamic as well. Most psychotropics are given per os, and the greater part of their absorption takes place in the small intestine. Premenopausal women have slower gastric emptying times and lower gastrointestinal blood flow which probably reduces the extent of drug absorption. The distribution of drugs is influenced by the relative lower body mass index, the lower blood volume and flow and the greater percentage of body fat of women...
April 2016: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/27444984/drug-interactions-between-hormonal-contraceptives-and-psychotropic-drugs-a-systematic-review
#18
Erin N Berry-Bibee, Myong-Jin Kim, Katharine B Simmons, Naomi K Tepper, Halley E M Riley, H Pamela Pagano, Kathryn M Curtis
OBJECTIVE: To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug. METHODS: We searched PubMed and Cochrane libraries for clinical or pharmacokinetic (PK) studies that examined co-administration of any HC with psychotropic drugs [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors (MAOIs), or atypical antipsychotics] in reproductive aged women...
July 18, 2016: Contraception
https://www.readbyqxmd.com/read/27440861/the-use-of-in-vitro-data-and-physiologically-based-pharmacokinetic-modeling-to-predict-drug-metabolite-exposure-desipramine-exposure-in-cytochrome-p4502d6-extensive-and-poor-metabolizers-following-administration-of-imipramine
#19
Hoa Q Nguyen, Ernesto Callegari, R Scott Obach
Major circulating drug metabolites can be as important as the drugs themselves in efficacy and safety, so establishing methods whereby exposure to major metabolites following administration of parent drug can be predicted is important. In this study, imipramine, a tricyclic antidepressant, and its major metabolite desipramine were selected as a model system to develop metabolite prediction methods. Imipramine undergoes N-demethylation to form the active metabolite desipramine, and both imipramine and desipramine are converted to hydroxylated metabolites by the polymorphic enzyme CYP2D6...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27402279/task-and-treatment-length-dependent-effects-of-vortioxetine-on-scopolamine-induced-cognitive-dysfunction-and-hippocampal-extracellular-acetylcholine-in-rats
#20
Alan L Pehrson, Todd M Hillhouse, Nasser Haddjeri, Renaud Rovera, Joseph H Porter, Arne Mørk, Gennady Smagin, Dekun Song, David Budac, Manuel Cajina, Connie Sanchez
Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission...
September 2016: Journal of Pharmacology and Experimental Therapeutics
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