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https://www.readbyqxmd.com/read/28097008/preclinical-findings-predicting-efficacy-and-side-effect-profile-of-ly2940094-an-antagonist-of-nociceptin-receptors
#1
Jeffrey M Witkin, Linda M Rorick-Kehn, Mark J Benvenga, Benjamin L Adams, Scott D Gleason, Karen M Knitowski, Xia Li, Steven Chaney, Julie F Falcone, Janice W Smith, Julie Foss, Kirsti Lloyd, John T Catlow, David L McKinzie, Kjell A Svensson, Vanessa N Barth, Miguel A Toledo, Nuria Diaz, Celia Lafuente, Alma Jiménez, Alfonso Benito, Conception Pedregal, Maria A Martínez-Grau, Anke Post, Michael A Ansonoff, John E Pintar, Michael A Statnick
Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide whose receptor is designated ORL1 or nociceptin receptor (NOP). We utilized a potent, selective, and orally bioavailable antagonist with documented engagement with NOP receptors in vivo to assess antidepressant- and anxiolytic-related pharmacological effects of NOP receptor blockade along with measures of cognitive and motor impingement. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) displayed antidepressant-like behavioral effects in the forced-swim test in mice, an effect absent in NOP (-/-) mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28091995/biodegradability-of-fluoxetine-mefenamic-acid-and-metoprolol-using-different-microbial-consortiums
#2
Yolanda Flores Velázquez, Petia Mijaylova Nacheva
The biodegradation of fluoxetine, mefenamic acid, and metoprolol using ammonium-nitrite-oxidizing consortium, nitrite-oxidizing consortium, and heterotrophic biomass was evaluated in batch tests applying different retention times. The ammonium-nitrite-oxidizing consortium presented the highest biodegradation percentages for mefenamic acid and metoprolol, of 85 and 64% respectively. This consortium was also capable to biodegrade 79% of fluoxetine. The heterotrophic consortium showed the highest ability to biodegrade fluoxetine reaching 85%, and it also had a high potential for biodegrading mefenamic acid and metoprolol, of 66 and 58% respectively...
January 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28089656/how-do-antidepressants-influence-the-bold-signal-in-the-developing-brain
#3
REVIEW
Julia J Harris, Clare Reynell
Depression is a highly prevalent life-threatening disorder, with its first onset commonly occurring during adolescence. Adolescent depression is increasingly being treated with antidepressants, such as fluoxetine. The use of medication during this sensitive period of physiological and cognitive brain development produces neurobiological changes, some of which may outlast the course of treatment. In this review, we look at how antidepressant treatment in adolescence is likely to alter neurovascular coupling and brain energy use and how these changes, in turn, affect our ability to identify neuronal activity changes between participant groups...
December 21, 2016: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#4
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28075471/alterations-in-splenic-function-and-gene-expression-in-mice-with-depressive-like-behavior-induced-by-exposure-to-corticosterone
#5
Heqin Zhan, Feng Huang, Fulin Yan, Zhenghang Zhao, Jixia Zhang, Taizhen Cui, Fan Yang, Guangfan Hai, Xiaoman Jia, Yongji Shi
Depressed patients present with increased cortisol levels and attenuated immune responses. However, little is known about the association between depression and the spleen, as this is the largest peripheral immune organ. In this study, we examined alterations in splenic function and gene expression in mice with depressive-like behavior, well as the expression of certain proteins in related pathways. A mouse model of depression was established with the use of corticosterone. Splenic function and histopathology were assessed using Wright and H&E staining...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28074989/-antidepressants-agents-in-breast-cancer-patients-using-tamoxifen-review-of-basic-and-clinical-evidence
#6
María Elisa Irarrázaval O, Leonardo Gaete G
Tamoxifen (Tmf), is a standard of care for women with estrogen receptor positive (ER+) breast cancer. Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Antidepressive agents (AD) are often prescribed to women with breast cancer not only for depression, but also for anxiety and hot flashes. Some AD are substrates or inhibitors of the Tmf metabolic pathway. Therefore there may be interactions when Tmf and AD are prescribed simultaneously. Oncologic protection afforded by Tmf may become less effective or null when AD are indicated, especially in poor metabolizing patients...
October 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28070247/effectiveness-of-cognitive-behavioral-therapy-and-fluoxetine-on-sexual-function-of-women-with-obsessive-compulsive-disorder-a-double-blind-randomized-controlled-trial
#7
Zahra Sabetnejad, Fatemeh Assarian, Abdollah Omidi, Mohammad Reza Najarzadegan
BACKGROUND: Obsessive compulsive disorder (OCD) is a mental health concern due to its various negative consequences, especially in sexual function. Therefore, the treatment of sexual dysfunction in women with OCD is important in order to improve the patient's marital function and mental health. OBJECTIVES: To compare the sexual behavior and sexual and marital satisfaction in women with obsessive-compulsive disorder (OCD) before and after treatment with fluoxetine and cognitive behavior therapy...
November 2016: Electronic Physician
https://www.readbyqxmd.com/read/28070119/ocd-like-behavior-is-caused-by-dysfunction-of-thalamo-amygdala-circuits-and-upregulated-trkb-erk-mapk-signaling-as-a-result-of-spred2-deficiency
#8
M Ullrich, M Weber, A M Post, S Popp, J Grein, M Zechner, H Guerrero González, A Kreis, A G Schmitt, N Üçeyler, K-P Lesch, K Schuh
Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling...
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28063712/the-psychoactive-pollutant-fluoxetine-compromises-antipredator-behaviour-in-fish
#9
Jake M Martin, Minna Saaristo, Michael G Bertram, Phoebe J Lewis, Timothy L Coggan, Bradley O Clarke, Bob B M Wong
Pharmaceuticals are increasingly being detected in aquatic ecosystems worldwide. Particularly concerning are pharmaceutical pollutants that can adversely impact exposed wildlife, even at extremely low concentrations. One such contaminant is the widely prescribed antidepressant fluoxetine, which can disrupt neurotransmission and behavioural pathways in wildlife. Despite this, relatively limited research has addressed the behavioural impacts of fluoxetine at ecologically realistic exposure concentrations. Here, we show that 28-day fluoxetine exposure at two ecologically relevant dosages-one representing low surface water concentrations and another representing high effluent flow concentrations-alters antipredator behaviour in Eastern mosquitofish (Gambusia holbrooki)...
January 4, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28063625/regulation-of-insulin-receptor-phosphorylation-in-the-brains-of-prenatally-stressed-rats-new-insight-into-the-benefits-of-antidepressant-drug-treatment
#10
Katarzyna Głombik, Joanna Ślusarczyk, Ewa Trojan, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
A growing body of evidence supports the involvement of disturbances in the brain insulin pathway in the pathogenesis of depression. On the other hand, data concerning the impact of antidepressant drug therapy on brain insulin signaling remain scare and insufficient. We determinated the influence of chronic treatment with antidepressant drugs (imipramine, fluoxetine and tianeptine) on the insulin signaling pathway of the brain of adult prenatally stressed rats. 3-month-old prenatally stressed and control rats were treated for 21 days with imipramine, fluoxetine or tianeptine (10mg/kg/day i...
January 4, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28052847/subcellular-partitioning-and-intra-macrophage-selectivity-of-antimicrobial-compounds-against-mycobacterium-tuberculosis
#11
Michael D Schump, Douglas M Fox, Carolyn R Bertozzi, Lee W Riley
The efficacy of antimicrobial drugs against Mycobacterium tuberculosis (Mtb), an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. However, inside of infected macrophages bacteria encounter an environment which differs substantially from broth culture and are subject to important host-dependent pharmacokinetic phenomena which modulate drug activity. Here we describe how pH dependent partitioning drives asymmetric antimicrobial drug distribution in Mtb infected macrophages...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28045461/antidepressant-responsiveness-in-adulthood-is-permanently-impaired-after-neonatal-destruction-of-the-neurogenic-pool
#12
S Yu, I Zutshi, R Stoffel, J Zhang, A P Ventura-Silva, N Sousa, P S Costa, F Holsboer, A Patchev, O F X Almeida
The dynamic turnover of hippocampal neurons is implicated in the regulation of cognitive and affective behavior. Extending our previous demonstration that administration of dexamethasone (ND) to neonatal rats depletes the resident population of neural precursor cells (NPC) and restrains the size of the neurogenic regions, we now show that the adverse effects of ND persist into adulthood. Specifically, ND impairs repletion of the neurogenic pool and neurogenesis; ND also compromises cognitive performance, the ability to actively adapt to an acute stressor and, the efficacy of glucocorticoid (GC) negative feedback...
January 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28045162/biochemical-effects-of-venlafaxine-on-astrocytes-as-revealed-by-1-h-nmr-based-metabolic-profiling
#13
Lu Sun, Liang Fang, Bin Lian, Jin-Jun Xia, Chan-Juan Zhou, Ling Wang, Qiang Mao, Xin-Fa Wang, Xue Gong, Zi-Hong Liang, Shun-Jie Bai, Li Liao, Yu Wu, Peng Xie
As a serotonin-norepinephrine reuptake inhibitor [SNRI], venlafaxine is one of the most commonly prescribed clinical antidepressants, with a broad range of antidepressant effects. Accumulating evidence shows that venlafaxine may target astrocytes to exert its antidepressant activity, although the underlying pharmacological mechanisms remained largely unknown. Here, we used a (1)H nuclear magnetic resonance (NMR)-based metabonomics method coupled with multivariate statistical analysis to characterize the metabolic profiling of astrocytes treated with venlafaxine to explore the potential mechanism of its antidepressant effect...
January 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28041791/activity-of-etv5a-and-etv5b-genes-in-the-hypothalamus-of-fasted-zebrafish-is-influenced-by-serotonin
#14
Alejandro S Mechaly, Ebony Richardson, Silke Rinkwitz
Serotonin has been implicated in the inhibition of food intake in vertebrates. However, the mechanisms through which serotonin acts has yet to be elucidated. Recently, ETV5 (ets variant gene 5) has been associated with obesity and food intake control mechanisms in mammals. We have analyzed a putative physiological function of the two etv5 paralogous genes (etv5a and etv5b) in neuronal food intake control in adult zebrafish that have been exposed to different nutritional conditions. A feeding assay was established and fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), was applied...
December 29, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28035393/fluoxetine-protects-against-methamphetamine%C3%A2-induced-lung-inflammation-by-suppressing-oxidative-stress-through-the-sert-p38-mapk-nrf2-pathway-in-rats
#15
Yun Wang, Yu-Han Gu, Ming Liu, Yang Bai, Huai-Liang Wang
Methamphetamine (MA) abuse is a major public health and safety concern throughout the world and a growing burden on healthcare costs. The purpose of the present study was to investigate the protective effect of fluoxetine against MA‑induced chronic pulmonary inflammation and to evaluate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidative stress. Wistar rats were divided into control, MA and two fluoxetine‑treated groups. Rats in the MA and the two fluoxetine‑treated groups were treated daily with intraperitoneal injection of 10 mg/kg MA twice daily...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28030789/the-ssri-fluoxetine-exhibits-mild-effects-on-the-reproductive-axis-in-the-cichlid-fish-cichlasoma-dimerus-teleostei-cichliformes
#16
Luciana S Dorelle, Rodrigo H Da Cuña, Graciela Rey Vázquez, Christian Höcht, Akio Shimizu, Griselda Genovese, Fabiana L Lo Nostro
Among the wide variety of pharmaceuticals released into the environment, Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is one of the most prescribed for the treatment of major depression. It inhibits serotonin (5-HT) reuptake at the presinaptic membrane, increasing serotonergic activity. In vertebrates, including fish, the serotonergic system is closely related to the Hypothalamic Pituitary Gonadal (HPG) axis which regulates reproduction. As FLX can act as an endocrine disrupting compound (EDC) by affecting several reproductive parameters in fish, the aim of this study was to provide an integral assessment of the potential effect of FLX on the reproductive axis of the Neotropical freshwater fish Cichlasoma dimerus...
December 25, 2016: Chemosphere
https://www.readbyqxmd.com/read/28029083/psychopathological-behaviour-and-cognition-in-morbid-obesity
#17
Alba Calderone, Pasquale Fabio Calabrò, Chita Lippi, Roberta Jaccheri, Jacopo Vitti, Ferruccio Santini
BACKGROUND: Obesity is a chronic condition with high prevalence and multifaceted aetiology, accompanied by an increased risk of morbidity and mortality. Obesity has several negative effects on the psychological status, and the severity of psychological disorders correlates with the degree of obesity. OBJECTIVE: Aim of this review is to provide an overview of the literature concerning the psychological distress associated with severe obesity, which contributes to deterioration of the quality of life of affected patients...
December 26, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
https://www.readbyqxmd.com/read/28028599/circadian-behavior-of-adult-mice-exposed-to-stress-and-fluoxetine-during-development
#18
Veronika Kiryanova, Victoria M Smith, Richard H Dyck, Michael C Antle
INTRODUCTION: Women of child-bearing age are the population at greatest risk for depression. The stress experienced during pregnancy and the associated antidepressant treatments can both affect fetal development. Fluoxetine (FLX) is among the most common antidepressants used by pregnant women. We have previously demonstrated that perinatal exposure to FLX can alter expression of circadian rhythms in adulthood. Here, we examine the combined effects of maternal stress during pregnancy and perinatal exposure to the antidepressant FLX on the circadian behavior of mice as adults...
December 27, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28025020/epigenetic-and-genetic-variants-in-the-htr1b-gene-and-clinical-improvement-in-children-and-adolescents-treated-with-fluoxetine
#19
Patricia Gassó, Natalia Rodríguez, Ana Blázquez, Ana Monteagudo, Daniel Boloc, Maria Teresa Plana, Amalia Lafuente, Luisa Lázaro, Joan Albert Arnaiz, Sergi Mas
The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine...
December 23, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28018840/hand-impairment-in-systemic-sclerosis-various-manifestations-and-currently-available-treatment
#20
Amber Young, Rajaie Namas, Carole Dodge, Dinesh Khanna
Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life...
September 2016: Current Treatment Options in Rheumatology
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