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https://www.readbyqxmd.com/read/28323425/structure-based-design-of-highly-selective-and-potent-g-protein-coupled-receptor-kinase-2-inhibitors-based-on-paroxetine
#1
Helen V Waldschmidt, Kristoff T Homan, Marilyn C Cato, Osvaldo Cruz-Rodríguez, Alessandro Cannavo, Michael W Wilson, Jianliang Song, Joseph Y Cheung, Walter J Koch, John J G Tesmer, Scott D Larsen
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure based drug design approach we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC50 of 30 nM against GRK2 and greater than 230-fold selectivity over other GRKs and kinases...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28319423/silexan-does-not-cause-withdrawal-symptoms-even-when-abruptly-discontinued
#2
M Gastpar, W E Müller, H P Volz, H J Möller, S Schläfke, A Dienel, S Kasper
OBJECTIVE: Subsequent to a randomised, double-blind, double dummy clinical trial assessing the efficacy of silexan compared to placebo and paroxetine in patients suffering from generalised anxiety disorder (GAD), a 1week follow-up phase was added in order to assess possible withdrawal symptoms of silexan after abrupt discontinuation. METHODS: Participants received silexan 80 mg/d, silexan 160 mg/d, paroxetine 20 mg/d, or placebo at a ratio of 1:1:1:1. Study medication was discontinued after the 10 week active treatment phase of the original trial...
March 20, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28315270/sigma-1-receptor-agonists-and-their-clinical-implications-in-neuropsychiatric-disorders
#3
Yakup Albayrak, Kenji Hashimoto
Accumulating evidence suggests that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some selective serotonin reuptake inhibitors (SSRIs). Among the SSRIs, the order of affinity for sigma-1 receptors is as follows: fluvoxamine > sertraline > fluoxetine > escitalopram > citalopram > paroxetine. Some SSRIs (e.g., fluvoxamine, fluoxetine and escitalopram) and other drugs (donepezil , ifenprodil , dehydroepiandeterone (DHEA)) potentiate nerve-growth factor (NGF)-induced neurite outgrowth in PC12 cells, and these effects could be antagonized by the selective sigma-1 receptor antagonist NE-100...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28301398/a-pilot-study-cardiac-parameters-in-children-receiving-new-generation-antidepressants
#4
Mai Uchida, Andrea E Spencer, Tara Kenworthy, James Chan, Maura Fitzgerald, Ana Maria Rosales, Elana Kagan, Alexandra Saunders, Joseph Biederman
OBJECTIVE: Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. STUDY DESIGN: The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine)...
March 15, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28286537/smoking-and-antidepressants-pharmacokinetics-a-systematic-review
#5
REVIEW
Pedro Oliveira, Joana Ribeiro, Helena Donato, Nuno Madeira
BACKGROUND: Despite an increasingly recognized relationship between depression and smoking, little is known about how smoking influences antidepressant response and treatment outcomes. The aim of this study was to systematically review the evidence of the impact of smoking on new-generation antidepressants with an emphasis on the pharmacokinetic perspective. METHODS: We present a systematic review of clinical trials comparing the serum levels of new-generation antidepressants in smokers and nonsmokers...
2017: Annals of General Psychiatry
https://www.readbyqxmd.com/read/28279926/determination-of-drugs-in-plasma-samples-by-disposable-pipette-extraction-with-c18-bsa-phase-and-liquid-chromatography-tandem-mass-spectrometry
#6
Mônia Ap Lemos Pinto, Israel D de Souza, Maria Eugênia C Queiroz
This work describes restricted access material (RAM) constituted of porous octadecylsilane particles with the outer surface covered with bovine serum albumin (C18-BSA) as a stationary phase to extract drugs from plasma samples by disposable pipette extraction (DPX) for further analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The C18-BSA phase simultaneously excluded macromolecules by chemical diffusion barrier (BSA network) and enrichment of the interior phase (C18) with drug traces by sorption...
March 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28275829/endothelial-nitric-oxide-synthase-in-rat-brain-is-downregulated-by-sub-chronic-antidepressant-treatment
#7
Yuta Yoshino, Shinichiro Ochi, Kiyohiro Yamazaki, Shunsuke Nakata, Jun-Ichi Iga, Shu-Ichi Ueno
BACKGROUND: Nitric oxide (NO) is a neurotransmitter that may be related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces a dose-dependent antidepressant-like effect. NO modulates major neurotransmitters involved in the neurobiology of MDD, such as norepinephrine, serotonin, dopamine, and glutamate. In this study, we investigated the effects of antidepressants as NO modulators in acute and sub-chronic treatments. METHODS: Rats were injected with the SSRI paroxetine (PAR, 10 mg/kg), the SNRI milnacipran (MIL, 30 mg/kg), or the NaSSA mirtazapine (MIR, 10 mg/kg) for acute (1 h) or sub-chronic (3 weeks) treatment prior to analysis of nine brain regions (frontal cortex, temporal cortex, striatum, thalamus, hippocampus, midbrain, pons, cerebellum, and olfactory bulb)...
March 8, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28262603/biological-profiling-of-prospective-antidepressant-response-in-major-depressive-disorder-associations-with-neuro-inflammation-fatty-acid-metabolism-and-amygdala-reactivity
#8
R J T Mocking, T S Nap, A M Westerink, J Assies, F M Vaz, M W J Koeter, H G Ruhé, A H Schene
BACKGROUND: A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown. PURPOSE: To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response...
February 21, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28260511/clinically-relevant-drug-interactions-with-anti-alzheimer-s-drugs
#9
Filippo Caraci, Janet Sultana, Filippo Drago, Edoardo Spina
The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD...
March 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28258931/the-effects-of-paroxetine-and-amitriptyline-on-the-upper-esophageal-sphincter-ues-pressure-and-its-natural-history-in-globus-pharyngeus
#10
Wen-Cong Zhou, Lin Jia, Dong-Yun Chen, Yao Liu, Jing Liu, Shu-Man Jiang, Meng Yang, Jian Xu
BACKGROUND: Antidepressant agents have been shown to be an effective and safe treatment method for patients with globus. However, there are few clinical trials dedicated to studying the effects of antidepressant agents on the natural history and upper oesophageal sphincter (UES) pressure of treated globus patients. AIMS: To evaluate the effect of paroxetine and amitriptyline to prevent relapses in patients with globus, the simultaneous relationship between changes in UES pressure and improvement of globus symptoms were measured...
February 28, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28258180/rare-case-of-severe-serotonin-syndrome-leading-to-bilateral-compartment-syndrome
#11
Verena Clarissa Samara, Judith Warner
The term 'serotonin syndrome' describes a constellation of symptoms caused by serotonergic overstimulation. Its characteristic clinical presentation consists of encephalopathy, neuromuscular signs and autonomic hyperactivity. After removal of the offending agent, the clinical course is usually self-limited but can occasionally lead to severe symptoms. We report the case of a 68-year-old woman who presented emergently with encephalopathy. Home medications included paroxetine and dextroamphetamine/amphetamine...
March 3, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28241064/meta-analyses-of-comparative-efficacy-of-antidepressant-medications-on-peripheral-bdnf-concentration-in-patients-with-depression
#12
Chanjuan Zhou, Jiaju Zhong, Bin Zou, Liang Fang, Jianjun Chen, Xiao Deng, Lin Zhang, Xiang Zhao, Zehui Qu, Yang Lei, Ting Lei
BACKGROUND: Brain derived neurotrophic factor (BDNF) is one of the most important regulatory proteins in the pathophysiology of major depressive disorder (MDD). Increasing numbers of studies have reported the relationship between serum/plasma BDNF and antidepressants (ADs). However, the potential effects of several classes of antidepressants on BDNF concentrations are not well known. Hence, our meta-analyses aims to review the effects of differential antidepressant drugs on peripheral BDNF levels in MDD and make some recommendations for future research...
2017: PloS One
https://www.readbyqxmd.com/read/28181177/outcomes-associated-with-generic-drugs-approved-using-product-specific-determinations-of-therapeutic-equivalence
#13
Joshua J Gagne, Jennifer M Polinski, Wenlei Jiang, Sarah K Dutcher, Jing Xie, Joyce Lii, Lisa A Fulchino, Aaron S Kesselheim
OBJECTIVE: We sought to examine rates of clinical outcomes among patients before and after market introduction of generic versions of five drugs approved using product-specific equivalence determinations. METHODS: We used data from a large national insurer to identify patients who initiated a study (acarbose tablets, salmon calcitonin nasal spray, enoxaparin injection, vancomycin capsules, venlafaxine extended-release tablets) or control drug (nateglinide, glimepiride, alendronate, fondaparinux, metronidazole, sertraline, paroxetine) in each calendar month between 2003 and 2012 and to determine rates of claims-based proxies for lack of effectiveness outcomes following initiation...
February 8, 2017: Drugs
https://www.readbyqxmd.com/read/28179152/the-six-most-widely-used-selective-serotonin-reuptake-inhibitors-decrease-androgens-and-increase-estrogens-in-the-h295r-cell-line
#14
Cecilie Hurup Hansen, Lizette Weber Larsen, Amalie Møller Sørensen, Bent Halling-Sørensen, Bjarne Styrishave
Selective serotonin reuptake inhibitors (SSRIs) used as first line of treatment in major depressive disorder (MDD) are known to exert negative effects on the endocrine system and fertility. The aim of the present study was to investigate the possible endocrine disrupting effect of six SSRIs, fluoxetine, paroxetine, citalopram and its active enantiomer escitalopram, sertraline and fluvoxamine using the OECD standardized and validated human in vitro adrenocortical H295R cell assay. All the major steroids, including progestagens, corticosteroids, androgens and estrogens were analysed using a fully validated LC-MS/MS method...
February 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28130988/single-and-multi-component-adsorption-of-psychiatric-pharmaceuticals-onto-alternative-and-commercial-carbons
#15
Vânia Calisto, Guilaine Jaria, Carla Patrícia Silva, Catarina I A Ferreira, Marta Otero, Valdemar I Esteves
This work describes the adsorptive removal of three widely consumed psychiatric pharmaceuticals (carbamazepine, paroxetine and oxazepam) from ultrapure water. Two different adsorbents were used: a commercial activated carbon and a non-activated waste-based carbon (PS800-150-HCl), produced by pyrolysis of primary paper mill sludge. These adsorbents were used in single, binary and ternary batch experiments in order to determine the adsorption kinetics and equilibrium isotherms of the considered pharmaceuticals...
January 25, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28123299/escitalopram-versus-paroxetine-controlled-release-in-major-depressive-disorder-a-randomized-trial
#16
Taro Kishi, Yuki Matsuda, Shinji Matsunaga, Masatsugu Moriwaki, Yoichiro Otake, Kaku Akamatsu, Tomo Okochi, Shigeki Hirano, Toshihiko Funahashi, Momoko Okuda, Hideaki Tabuse, Kiyoshi Fujita, Nakao Iwata
OBJECTIVE: There are no direct comparisons between escitalopram and paroxetine controlled release in patients with major depressive disorder (MDD). METHODS: We conducted a 24-week, rater-masked, randomized trial of escitalopram (5-20 mg/day) versus paroxetine controlled release (12.5-50 mg/day) in patients with MDD (UMIN000011191). Patients with the diagnosis of moderate-to-severe MDD (a 17-item Hamilton Rating Scale for Depression [HAMD-17], with total score at baseline being ≥20) were recruited to participate in a parallel, randomized, controlled trial...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28101753/effect-and-safety-of-paroxetine-combined-with-zolpidem-in-treatment-of-primary-insomnia
#17
Z H Yu, X H Xu, S D Wang, M F Song, Y Liu, Y Yin, H J Mao, G Z Tang
PURPOSE: Primary insomnia is a persistent and recurrent disorder as well as a risk factor for depression. The aim of this study was to determine whether the zolpidem combined with paroxetine would be effective in the treatment of patients with primary insomnia. METHODS: Ninety patients meeting DSM-IV criteria for primary insomnia were randomly assigned to 8 weeks of treatment with zolpidem combined with paroxetine (the combined treatment group, n = 45) or zolpidem combined with placebo (the control group, n = 45)...
January 18, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28096676/aripiprazole-augmentation-in-managing-comorbid-obsessive-compulsive-disorder-and-bipolar-disorder-a-case-with-suicidal-attempts
#18
Jianbo Lai, Qiaoqiao Lu, Peng Zhang, Tingting Xu, Yi Xu, Shaohua Hu
Comorbid obsessive-compulsive disorder (OCD) and bipolar disorder (BD) have long been an intractable problem in clinical practice. The increased risk of manic/hypomanic switch hinders the use of antidepressants for managing coexisting OCD symptoms in BD patients. We herein present a case of a patient with BD-OCD comorbidity, who was successfully treated with mood stabilizers and aripiprazole augmentation. The young female patient reported recurrent depressive episodes and aggravating compulsive behaviors before hospitalization...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28089628/crf1-but-not-glucocorticoid-receptor-antagonists-reduce-separation-induced-distress-vocalizations-in-guinea-pig-pups-and-crf-overexpressing-mouse-pups-a-combination-study-with-paroxetine
#19
P Monika Verdouw, Joantine C J van Esterik, Bernard W M M Peeters, Mark J Millan, Lucianne Groenink
RATIONALE: Given the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment. OBJECTIVES: We evaluated the anxiolytic effects of corticotropin releasing factor (CRF)1 receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI)...
March 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28088261/parquetina-nigrescens-leaves-chemical-profile-and-influence-on-the-physical-and-biochemical-indices-of-sexual-activity-of-male-wistar-rats
#20
Omowumi Titilola Kayode, Musa Toyin Yakubu
OBJECTIVE: The leaves of Parquetina nigrescens have been claimed in folk medicine to be useful for managing sexual dysfunction, but there is inadequate scientific evidence for this claim. This investigation was conducted to assess the effects of aqueous leaf extract of Parquetina nigrescens (AEPN) in rats induced with sexual dysfunction. METHODS: Male rats were allocated into various groups after being induced into sexual dysfunction with paroxetine hydrochloride...
January 2017: Journal of Integrative Medicine
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