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https://www.readbyqxmd.com/read/28817365/effect-of-flibanserin-treatment-on-body-weight-in-premenopausal-and-postmenopausal-women-with-hypoactive-sexual-desire-disorder-a-post-hoc-analysis
#1
Susan G Kornstein, James A Simon, Stuart C Apfel, James Yuan, Krista A Barbour, Robert Kissling
BACKGROUND: Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the effect of flibanserin treatment on body weight in premenopausal and postmenopausal women with HSDD. MATERIALS AND METHODS: This analysis included three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg each bedtime (qhs) in premenopausal women, a similarly designed study in postmenopausal women, and a 52-week, open-label extension study in premenopausal women...
August 17, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28815279/evaluation-of-training-dose-in-male-sprague-dawley-rats-trained-to-discriminate-4-methylmethcathinone
#2
Michael D Berquist, Nathyn A Thompson, Lisa E Baker
RATIONALE: Although the synthetic cathinone 4-methylmethcathinone (4-MMC, mephedrone) has been a subject of intensive research investigation, the pharmacological mechanisms involved in its interoceptive stimulus effects have yet to be fully characterized. OBJECTIVE: The present study employed drug discrimination methods in rats to compare the interoceptive stimulus properties of two different training doses of 4-MMC to other substances with similar pharmacological actions...
August 16, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28806488/serotonergic-5-ht2b-receptors-in-mitral-valvulopathy-bone-marrow-mobilization-of-endothelial-progenitors
#3
Estelle Ayme-Dietrich, Roland Lawson, Francine Côté, Claudia de Tapia, Sylvia Da Silva, Claudine Ebel, Béatrice Hechler, Christian Gachet, Jérome Guyonnet, Hélène Rouillard, Jordane Stoltz, Emily Quentin, Sophie Banas, François Daubeuf, Nelly Frossard, Bernard Gasser, Jean-Philippe Mazzucotelli, Olivier Hermine, Luc Maroteaux, Laurent Monassier
BACKGROUND: Valvular heart disease is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the serotonin system has been associated with valvular heart disease. PURPOSE AND EXPERIMENTAL APPROACH: Here, we investigated the contribution of serotonin receptors in a mouse model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens dexfenfluramine and benfluorex. KEY RESULTS: Chronically activated 5-HT2B receptors by nordexfenfluramine in mice mimicked early steps of mitral valve remodelling attested by increased valve thickness, and cell density in a thick extracellular matrix...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28796998/microrna-dependent-control-of-serotonin-induced-pulmonary-arterial-contraction
#4
Diana Dahan, Tran Thi Hien, Philip Tannenberg, Mari Ekman, Catarina Rippe, Thomas Boettger, Thomas Braun, Karin Tran-Lundmark, Phan-Kiet Tran, Karl Swärd, Sebastian Albinsson
BACKGROUND: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. METHODS: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. RESULTS: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced...
August 11, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28795258/lipopolysaccharide-aggravated-doi-induced-tourette-syndrome-elaboration-for-recurrence-of-tourette-syndrome
#5
Long Hongyan, Si Zhenyang, Wang Chunyan, Pan Qingqing
Tourette syndrome (TS) is a neurological disorder characterized by highest familial recurrence rate among neuropsychiatric diseases with complicated inheritance. Recurrence of Tourette syndrome was frequently observed in clinical. Unexpectedly, the mechanism of recurrence of Tourette syndrome was failure to elucidate. Here, we first shown that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome. The TS model in rats was induced by DOI (the selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl) -2- aminopropane)...
August 9, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28790887/mir-16-and-fluoxetine-both-reverse-autophagic-and-apoptotic-change-in-chronic-unpredictable-mild-stress-model-rats
#6
Yang Yang, Zhiying Hu, Xiaoxue Du, Henry Davies, Xue Huo, Marong Fang
In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28790021/deficient-striatal-adaptation-in-aminergic-and-glutamatergic-neurotransmission-is-associated-with-tardive-dyskinesia-in-non-human-primates-exposed-to-antipsychotic-drugs
#7
Catherine Lévesque, Giovanni Hernandez, Souha Mahmoudi, Frédéric Calon, Fabrizio Gasparini, Baltazar Gomez-Mancilla, Pierre J Blanchet, Daniel Lévesque
Tardive dyskinesia (TD) is a potentially disabling condition encompassing all delayed, persistent, and often irreversible abnormal involuntary movements arising in a fraction of subjects during long-term exposure to centrally acting dopamine receptor-blocking agents such as antipsychotic drugs and metoclopramide. However, the pathogenesis of TD has proved complex and remains elusive. To investigate the mechanism underlying the development of TD, we have chronically exposed 17 Cebus apella monkeys to typical (11) or atypical (6) antipsychotic drugs...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28783139/antipsychotic-induced-hdac2-transcription-via-nf-%C3%AE%C2%BAb-leads-to-synaptic-and-cognitive-side-effects
#8
Daisuke Ibi, Mario de la Fuente Revenga, Nebojsa Kezunovic, Carolina Muguruza, Justin M Saunders, Supriya A Gaitonde, José L Moreno, Maryum K Ijaz, Vishaka Santosh, Alexey Kozlenkov, Terrell Holloway, Jeremy Seto, Aintzane García-Bea, Mitsumasa Kurita, Grace E Mosley, Yan Jiang, Daniel J Christoffel, Luis F Callado, Scott J Russo, Stella Dracheva, Juan F López-Giménez, Yongchao Ge, Carlos R Escalante, J Javier Meana, Schahram Akbarian, George W Huntley, Javier González-Maeso
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-κB repressor IκBα...
August 7, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28782490/unmet-needs-in-schizophrenia
#9
Maurizio Pompili, Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
August 3, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28782175/the-mechanism-of-acute-fasting-induced-antidepressant-like-effects-in-mice
#10
Ranji Cui, Jie Fan, Tongtong Ge, Linda Tang, Bingjin Li
Acute fasting induced antidepressant-like effects. However, the exact brain region and mechanism of these actions are still largely unknown. Therefore, in this study the antidepressant-like effects of acute fasting on c-Fos expression and BDNF levels were investigated. Consistent with our previous findings, immobility time was remarkably shortened by 9 hrs fasting in the forced swimming test. Furthermore, these antidepressant-like effects of 9 fasting were inhibited by a 5-HT2A/2C receptor agonist (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), and the effect of DOI was blocked by pretreatment with a selective 5-HT2A receptor antagonist ketanserin...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28780039/disruption-of-5-ht2a-pdz-protein-interaction-differently-affects-the-analgesic-efficacy-of-ssri-snri-and-tca-in-the-treatment-of-traumatic-neuropathic-pain-in-rats
#11
Anne-Sophie Wattiez, Amandine Dupuis, Anne-Marie Privat, Maryse Chalus, Eric Chapuy, Youssef Aissouni, Alain Eschalier, Christine Courteix
Antidepressants remain one of the first line treatments prescribed to neuropathic pain patients despite their limited efficacy and/or their numerous side effects. More and more, pharmacotherapy for neuropathic pain has evolved towards the use of therapeutic combinations. The goal of the present study was to assess the efficacy of the combination of antidepressants - selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors-with a peptide (TAT-2ASCV) able to disrupt the interaction between serotonin type 2A (5-HT2A) receptors and associated PDZ proteins...
August 2, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28777821/anatomy-and-behavioral-function-of-serotonin-receptors-in-drosophila-melanogaster-larvae
#12
Annina Huser, Melanie Eschment, Nazli Güllü, Katharina A N Collins, Kathrin Böpple, Lyubov Pankevych, Emilia Rolsing, Andreas S Thum
The biogenic amine serotonin (5-HT) is an important neuroactive molecule in the central nervous system of the majority of animal phyla. 5-HT binds to specific G protein-coupled and ligand-gated ion receptors to regulate particular aspects of animal behavior. In Drosophila, as in many other insects this includes the regulation of locomotion and feeding. Due to its genetic amenability and neuronal simplicity the Drosophila larva has turned into a useful model for studying the anatomical and molecular basis of chemosensory behaviors...
2017: PloS One
https://www.readbyqxmd.com/read/28774576/synthesis-and-biological-investigation-of-tetrahydropyridopyrimidinone-derivatives-as-potential-multireceptor-atypical-antipsychotics
#13
Hainimu Xiamuxi, Zhen Wang, Jianfeng Li, Yu Wang, Chunhui Wu, Feipu Yang, Xiangrui Jiang, Yongjian Liu, Qingjie Zhao, Weiming Chen, Jian Zhang, Yuanchao Xie, Tianwen Hu, Mingshuo Xu, Shuang Guo, Haji Akber Aisa, Yang He, Jingshan Shen
In the present study, a series of tetrahydropyridopyrimidinone derivatives, possessing potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (10d) held the best pharmacological profile. It not only exhibited potent and balanced activities for D2, 5-HT1A, and 5-HT2A receptors, but was also endowed with low activities for α1A, 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity for inducing orthostatic hypotension, weight gain and QT prolongation...
July 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28766351/the-impact-of-sleep-deprivation-on-hippocampal-mediated-learning-and-memory-in-rats
#14
M Saygin, M F Ozguner, O Onder, D K Doguc, I Ilhan, Y Peker
BACKGROUND: To examine the impact of different types of sleep deprivation on hippocampal-mediated learning and memory in rats. METHODS: Forty-eight Sprague-Dawley male rats were randomly assigned to 1 of 4 equal-size groups: (1) 12 hours of sleep per day (control). (2) total sleep deprivation (TSD), (3) rapid eye movement (REM) deprivation (RD), and (4) sleep restricted to 4 hours per day (SR). All rats were subjected to swimming training in the Morris water maze (MWM)...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28766260/erratum-to-mdma-induced-indifference-to-negative-sounds-is-mediated-by-the-5-ht2a-receptor
#15
K P C Kuypers, R de la Torre, M Farre, N Pizarro, L Xicota, J G Ramaekers
No abstract text is available yet for this article.
August 1, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28758583/new-trends-in-the-treatment-of-schizophrenia
#16
Herbert Y Meltzer
The objectives of this article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. RESULTS: Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine-type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects is becoming appreciated...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28750582/efficacy-and-safety-of-min-101-a-12-week-randomized-double-blind-placebo-controlled-trial-of-a-new-drug-in-development-for-the-treatment-of-negative-symptoms-in-schizophrenia
#17
Michael Davidson, Jay Saoud, Corinne Staner, Nadine Noel, Elisabeth Luthringer, Sandra Werner, Joseph Reilly, Jean-Yves Schaffhauser, Jonathan Rabinowitz, Mark Weiser, Remy Luthringer
OBJECTIVE: The authors assessed the efficacy, safety, and tolerability of MIN-101, a compound with affinities for sigma-2 and 5-HT2A receptors and no direct dopamine affinities, in comparison with placebo in treating negative symptoms in stabilized patients with schizophrenia. METHOD: The trial enrolled 244 patients who had been symptomatically stable for at least 3 months and had scores of at least 20 on the negative subscale of the Positive and Negative Syndrome Scale (PANSS)...
July 28, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28750135/ameliorative-effect-of-chlorpromazine-hydrochloride-on-visceral-hypersensitivity-in-rats-possible-involvement-of-5-ht2a-receptor
#18
Teita Asano, Ken-Ichiro Tanaka, Arisa Tada, Hikaru Shimamura, Rikako Tanaka, Hiroki Maruoka, Tohru Mizushima, Mitsuko Takenaga
BACKGROUND AND PURPOSE: Visceral hypersensitivity is responsible for pathogenesis of irritable bowel syndrome (IBS). Therefore, its prevention can help avoid abdominal pain and discomfort in IBS. To find candidate drugs for visceral hypersensitivity, we screened existing medicines for their ability to prevent visceral sensitivity induced by colorectal distension (CRD) in rats and identified chlorpromazine, a typical antipsychotic drug, as a candidate compound. In this study, we investigated the effect of chlorpromazine on visceral hypersensitivity...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28744219/mdma-induced-dissociative-state-not-mediated-by-the-5-ht2a-receptor
#19
Drew J Puxty, Johannes G Ramaekers, Rafael de la Torre, Magí Farré, Neus Pizarro, Mitona Pujadas, Kim P C Kuypers
Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28741031/inhibition-of-serotonin-transporters-disrupts-the-enhancement-of-fear-memory-extinction-by-3-4-methylenedioxymethamphetamine-mdma
#20
Matthew B Young, Seth D Norrholm, Lara M Khoury, Tanja Jovanovic, Sheila A M Rauch, Collin M Reiff, Boadie W Dunlop, Barbara O Rothbaum, Leonard L Howell
RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population...
July 24, 2017: Psychopharmacology
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