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https://www.readbyqxmd.com/read/28821667/fibroblast-growth-factor-2-in-the-dorsomedial-striatum-is-a-novel-positive-regulator-of-alcohol-consumption
#1
Oren Even-Chen, Yossi Sadot-Sogrin, Ohad Shaham, Segev Barak
Repeated alcohol intake leads to mesostriatal neuroadaptations, resulting in drinking escalation and addiction phenotypes. Fibroblast growth factor 2 (FGF2) has been shown to interact with the mesostriatal dopaminergic system, and has been implicated in the actions of psychostimulants in the brain, and in several psychiatric disorders. Here, we report on a positive regulatory feedback loop of alcohol and FGF2 in rodent models. Specifically, we found that acute alcohol exposure (2.5 g/kg, i.p.) increased the mRNA expression of Fgf2 in the dorsal hippocampus, nucleus accumbens and dorsal striatum...
August 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821448/cognitive-impairment-and-gene-expression-alterations-in-a-rodent-model-of-binge-eating-disorder
#2
A Chawla, Z A Cordner, G Boersma, T H Moran
Binge eating disorder (BED) is defined as recurrent, distressing over-consumption of palatable food (PF) in a short time period. Clinical studies suggest that individuals with BED may have impairments in cognitive processes, executive functioning, impulse control, and decision-making, which may play a role in sustaining binge eating behavior. These clinical reports, however, are limited and often conflicting. In this study, we used a limited access rat model of binge-like behavior in order to further explore the effects of binge eating on cognition...
August 15, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28818747/antidepressant-like-activity-of-methyl-jasmonate-involves-modulation-of-monoaminergic-pathways-in-mice
#3
Solomon Umukoro, Adaeze Adebesin, Gladys Agu, Osarume Omorogbe, Stephen Babajide Asehinde
PURPOSE: The efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study. MATERIALS AND METHODS: Mice were given i...
August 14, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28812124/clozapine-chlorpromazine-and-risperidone-dose-dependently-reduce-emotional-hyperthermia-a-biological-marker-of-salience
#4
William W Blessing, Esther M Blessing, Mazher Mohammed, Youichirou Ootsuka
RATIONALE: We recently introduced a new rat model of emotional hyperthermia in which a salient stimulus activates brown adipose tissue (BAT) thermogenesis and tail artery constriction. Antipsychotic drugs, both classical and second generation, act to reduce excessive assignment of salience to objects and events in the external environment. The close association between salient occurrences and increases in body temperature suggests that antipsychotic drugs may also reduce emotional hyperthermia...
August 15, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28807673/gpr55-a-therapeutic-target-for-parkinson-s-disease
#5
Marta Celorrio, Estefanía Rojo-Bustamante, Diana Fernández-Suárez, Elena Sáez, Ander Estella-Hermoso de Mendoza, Christa E Müller, María J Ramírez, Julen Oyarzábal, Rafael Franco, María S Aymerich
The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases. In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson's disease (PD)...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28805144/a-qm-protein-ligand-investigation-of-anti-psychotic-drugs-with-the-dopamine-d2-receptor-d2r
#6
Ramin Ekhteiari Salmas, Yusuf Serhat Is, Serdar Durdagi, Matthias Stein, Mine Yurtsever
The dopamine D2 Receptor (D2R) is a member of the G-Protein Coupled Receptor (GPCR) family and plays a critical role in neurotransmission activities in the human brain. Dysfunction in dopamine receptor signaling may lead to mental health illnesses such as schizophrenia and Parkinson's disease. D2R is the target protein of the commonly used anti-psychotic drugs such as risperidone, clozapine, aripiprazole, olanzapine, ziprasidone and quetiapine. Due to their significant side effects and nonselective profiles, the discovery of novel drugs has become a challenge for researchers working in this field...
August 14, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28801916/adenosine-and-dopamine-oppositely-modulate-a-hyperpolarization-activated-current-ih-in-chemosensory-neurons-of-the-rat-carotid-body-in-co-culture
#7
Min Zhang, Cathy Vollmer, Colin A Nurse
Adenosine and dopamine (DA) act as neurotransmitters or neuromodulators at the carotid body (CB) chemosensory synapse, however, their mechanisms of action are not fully understood. Using a functional co-culture model of rat CB chemoreceptor (type I) cell clusters and juxtaposed afferent petrosal neurons (PNs), we tested the hypothesis that adenosine and DA act postsynaptically to modulate a hyperpolarization-activated, cyclic nucleotide-gated (HCN) cation current (Ih ). In whole-cell recordings from hypoxia-responsive PNs, cAMP mimetics enhanced Ih whereas the HCN blocker ZD7288 (2 μm) reversibly inhibited Ih ...
August 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28801850/amisulpride-in-the-prevention-of-nausea-and-vomiting-induced-by-cisplatin-based-chemotherapy-a-dose-escalation-study
#8
Jørn Herrstedt, Yvonne Summers, Gedske Daugaard, Thomas B Christensen, Karin Holmskov, Paul D Taylor, Gabriel M Fox, Alexander Molassiotis
PURPOSE: The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy. METHODS: This dose-finding, non-comparative study investigated the antiemetic effect and safety of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0-24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron...
August 11, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28795477/exogenous-serotonin-regulates-colorectal-motility-via-the-5-ht2-and-5-ht3-receptors-in-the-spinal-cord-of-rats
#9
H Nakamori, K Naitou, Y Sano, H Shimaoka, T Shiina, Y Shimizu
BACKGROUND: We previously reported that intrathecal injection of noradrenaline or dopamine causes enhancement of colorectal motility. As these monoamines are neurotransmitters of descending pain inhibitory pathways in the spinal cord, we hypothesized that serotonin, which is one of the neurotransmitters involved in descending pain inhibition, also influences the lumbosacral defecation center. Therefore, we examined whether serotonin acting on the spinal defecation center enhances colorectal motility...
August 10, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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
#10
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/28782490/unmet-needs-in-schizophrenia
#11
Maurizio Pompili, Gloria Giordano, Mario Luciano, Valeria Del Vecchio, Gianluca Serafini, Gaia Sampogna, Denise Erbuto, Peter Falkai, Andrea Fiorillo
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/28774576/synthesis-and-biological-investigation-of-tetrahydropyridopyrimidinone-derivatives-as-potential-multireceptor-atypical-antipsychotics
#12
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/28758583/new-trends-in-the-treatment-of-schizophrenia
#13
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/28757247/l-dopa-inhibits-excitatory-synaptic-transmission-in-the-rat-nucleus-tractus-solitarius-through-release-of-dopamine
#14
Y Ohi, D Kodama, A Haji
The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1μM) was ineffective on the mEPSCs, and the highest concentration (100μM) exerted a stronger inhibitory effect. L-DOPA (10μM) decreased the amplitude of EPSCs (eEPSCs) evoked by electrical stimulation of the tractus solitarius and increased the paired-pulse ratio...
July 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28757154/the-central-serotonin2b-receptor-as-a-new-pharmacological-target-for-the-treatment-of-dopamine-related-neuropsychiatric-disorders-rationale-and-current-status-of-research
#15
REVIEW
Céline Devroye, Adeline Cathala, Pier Vincenzo Piazza, Umberto Spampinato
The serotonin2B receptor (5-HT2BR), which was first cloned and characterized in the rat stomach fundus, is the most recent addition to the 5-HT2R family. While its involvement in the regulation of gastrointestinal, vascular, pulmonary and cardiac physiology has been widely investigated, its functional role within the central nervous system (CNS) has received much less attention. Nevertheless, when considering the data available in the literature with regards to the regulatory control exerted by the central 5-HT2BR on dopamine (DA) and serotonin (5-HT) neuron activity, a very interesting picture emerges and highlights the key role of these receptors for future therapeutic strategies of DA-related neuropsychiatric disorders...
July 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28755886/pharmacological-profile-of-mephedrone-analogs-and-related-new-psychoactive-substances
#16
REVIEW
Dino Luethi, Karolina E Kolaczynska, Luca Docci, Stephan Krähenbühl, Marius C Hoener, Matthias E Liechti
BACKGROUND: Mephedrone is a synthetic cathinone and one of the most popular recreationally used new psychoactive substances. The aim of the present study was to characterize the in vitro pharmacology of novel analogs of mephedrone and related newly emerged designer stimulants. METHODS: We determined norepinephrine, dopamine, and serotonin transporter inhibition potencies and monoamine release in transporter-transfected human embryonic kidney 293 cells. We also assessed monoamine receptor and transporter binding affinities...
July 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28755876/a-computational-network-analysis-based-on-targets-of-antipsychotic-agents
#17
Lei Gao, Shuo Feng, Zhao-Yuan Liu, Jiu-Qiang Wang, Ke-Ke Qi, Kai Wang
Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum...
July 26, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28751068/dopa-decarboxylase-modulates-tau-toxicity
#18
Rebecca L Kow, Carl Sikkema, Jeanna M Wheeler, Charles W Wilkinson, Brian C Kraemer
BACKGROUND: The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D2-family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. METHODS: To better understand how loss of D2-family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects...
June 15, 2017: Biological Psychiatry
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
#19
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
#20
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
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