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https://www.readbyqxmd.com/read/28531264/cariprazine-exhibits-anxiolytic-and-dopamine-d3-receptor-dependent-antidepressant-effects-in-the-chronic-stress-model
#1
Vanya Duric, Mounira Banasr, Tina Franklin, Ashley Lepack, Nika Adham, Béla Kiss, István Gyertyán, Ronald S Duman
Background: Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the US for the treatment of schizophrenia and bipolar mania. We recently demonstrated that cariprazine also has significant anti-anhedonic-like effects in rats subjected to chronic stress; however, the exact mechanism of action for cariprazine's antidepressant-like properties is not known. Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28528402/impact-of-brown-rice-specific-%C3%AE-oryzanol-on-epigenetic-modulation-of-dopamine-d2-receptors-in-brain-striatum-in-high-fat-diet-induced-obesity-in-mice
#2
Chisayo Kozuka, Tadashi Kaname, Chigusa Shimizu-Okabe, Chitoshi Takayama, Masato Tsutsui, Masayuki Matsushita, Keiko Abe, Hiroaki Masuzaki
AIMS/HYPOTHESIS: Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#3
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28525823/development-and-validation-of-a-reversed-phase-hplc-method-for-analysis-of-radiochemical-purity-in-123-i-ibzm
#4
Shiou-Shiow Farn, Yuen-Han Yeh, Chang-Chin Li, Ching-Shiuann Yang, Jenn-Tzong Chen, Chung-Shan Yu, Wuu-Jyh Lin
[(123)I]IBZM is used widely for in vivo imaging of D2 receptors in human brain and shows relatively fast kinetics and a greater susceptibility to synaptic dopamine release than other single-photon emission computed tomography (SPECT) radioligands. A reliable and reversed-phase HPLC method using UV/VIS and radiometric detectors has been developed for qualitative analysis of BZM and IBZM and radiochemical purity in [(123)I]IBZM preparations. The method uses gradient elution on a Zorbax XDB C-18 column with a mobile phase that consists of 10mM 3,3-dimethylglutaric acid (DMGA), pH 7...
April 15, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28522735/d3-receptors-regulate-excitability-in-a-unique-class-of-prefrontal-pyramidal-cell
#5
Rebecca L Clarkson, Alayna T Liptak, Steven M Gee, Vikaas S Sohal, Kevin J Bender
The D3 dopamine receptor, a member of the Gi-coupled D2-family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex. These receptors are important for prefrontal executive function, as pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. And yet, the mechanisms by which D3 receptors regulate prefrontal circuits, and whether D3 receptors regulate specific prefrontal subnetworks, remain unknown...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522313/neurotensin-in-the-nucleus-accumbens-reverses-dopamine-supersensitivity-evoked-by-antipsychotic-treatment
#6
Alice Servonnet, Ellie-Anna Minogianis, Claude Bouchard, Anne-Marie Bédard, Daniel Lévesque, Pierre-Paul Rompré, Anne-Noël Samaha
Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine...
May 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28521372/synthesis-and-characterization-of-new-azecine-derivatives-as-potential-neuroleptics
#7
Stephanie Zergiebel, Christian Fleck, Hans-Dieter Arndt, Christoph Enzensperger, Andreas Seeling
Dibenzo- and benzindolo-azecines represent a class of potential neuroleptics. To characterize the effectiveness at the dopamine and 5-HT2A-receptor representative structures were synthesized and tested by radio ligand binding studies, in vivo and in vitro studies.Neuroleptic potency and the risk of side effects of the prodrug 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-yl isobutyrate, an ester derivative of the most promising azecine 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-ol (LE404), was tested in vivo concerning conditioned avoidance response inhibition, locomotor activity and triggering of catalepsy vs...
May 18, 2017: Drug Research
https://www.readbyqxmd.com/read/28516430/ramelteon-improves-post-traumatic-stress-disorder-like-behaviors-exhibited-by-fatty-acid-binding-protein-3-null-mice
#8
Yasushi Yabuki, Ibuki Takahata, Kazuya Matsuo, Yuji Owada, Kohji Fukunaga
We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 (-/-)) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2 receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably, chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3 (-/-) mice...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515684/selegiline-ameliorates-depression-like-behavior-in-mice-lacking-the-cd157-bst1-gene-a-risk-factor-for-parkinson-s-disease
#9
Satoka Kasai, Toru Yoshihara, Olga Lopatina, Katsuhiko Ishihara, Haruhiro Higashida
Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28514338/-a-comparative-chemoreactome-analysis-of-mexidol
#10
I Yu Torshin, O A Gromova, I S Sardaryan, L E Fedotova
AIM: To compare mexidol with control molecules (choline alfoscerate, piracetam, glycine, semax) using chemoreactome analysis. MATERIAL AND METHODS: The chemical structure of mexidol was compared to molecule metabolites extracted from the Human Metabolome Database (HMDB) and a drug database. More than 40 000 of metabolites from HMDB were used as a model of human metabolome. RESULTS AND CONCLUSION: The chemoreactome analysis showed that mexidol may be (1) an agonist of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the effects of which are carried out by inhibiting the synthesis of pro-inflammatory prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28509598/elevated-dopamine-d1-receptor-availability-in-striatum-of-g%C3%A3-ttingen-minipigs-after-electroconvulsive-therapy
#11
Anne M Landau, Aage Ko Alstrup, Helene Audrain, Steen Jakobsen, Mette Simonsen, Arne Møller, Poul Videbech, Gregers Wegener, Albert Gjedde, Doris J Doudet
Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [(11)C]SCH23390...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28507584/effects-of-adenosine-receptor-antagonists-in-mptp-mouse-model-of-parkinson-s-disease-mitochondrial-dna-integrity
#12
Soha S Essawy, Mona Kamal Tawfik, Horya Erfan Korayem
INTRODUCTION: In Parkinson's disease (PD), compelling data indicate a functional link between adenosine/dopamine receptors and the progression of the neurodegenerative process. The present study was carried out to evaluate the effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an ADRsA1 antagonist, and ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002), an ADRsA2A antagonist, on the prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice...
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28507321/pet-imaging-of-dopamine-d2-receptor-internalization-in-schizophrenia
#13
J J Weinstein, E van de Giessen, R J Rosengard, X Xu, N Ojeil, G Brucato, R B Gil, L S Kegeles, M Laruelle, M Slifstein, A Abi-Dargham
Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28499973/activation-of-dopamine-d1-receptors-enhances-the-temporal-summation-and-excitability-of-rat-retinal-ganglion-cells
#14
Peng Cui, Xue-Yan Li, Yuan Zhao, Qian Li, Feng Gao, Ling-Zhu Li, Ning Yin, Xing-Huai Sun, Zhongfeng Wang
Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28495376/gabaa-receptor-positive-allosteric-modulators-modify-the-abuse-related-behavioral-and-neurochemical-effects-of-methamphetamine-in-rhesus-monkeys
#15
Laís F Berro, Monica L Andersen, Sergio Tufik, Leonard L Howell
GABAA receptor positive allosteric modulators (GABAA receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABAA receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABAA receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5)...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28490648/randomized-trial-of-preladenant-given-as-monotherapy-in-patients-with-early-parkinson-disease
#16
Fabrizio Stocchi, Olivier Rascol, Robert A Hauser, Susan Huyck, Anjela Tzontcheva, Rachel Capece, Tony W Ho, Peter Sklar, Christopher Lines, David Michelson, David J Hewitt
OBJECTIVE: To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. METHODS: This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo...
May 10, 2017: Neurology
https://www.readbyqxmd.com/read/28489950/the-return-of-d4-dopamine-receptor-antagonists-in-drug-discovery
#17
Craig W Lindsley, Corey R Hopkins
The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Coupled with genetic association of the DRD4 gene with various CNS disorders, multiple companies launched discovery programs to develop selective D4 antagonists. Merck's D4 antagonist L-745,870 was the first to reach the clinic, where it was found to be ineffective in schizophrenia patients, and other groups failed to recapitulate some of the genetic data...
May 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28487067/selective-and-interactive-effects-of-d2-receptor-antagonism-and-positive-allosteric-mglur4-modulation-on-waiting-impulsivity
#18
Sarah N Isherwood, Trevor W Robbins, Janet R Nicholson, Jeffrey W Dalley, Anton Pekcec
BACKGROUND: Metabotropic glutamate receptor 4 (mGluR4) and dopamine D2 receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D2 receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D2 receptor antagonist eticlopride, on two distinct forms of impulsivity...
May 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28486094/a-pharmacodynamic-modelling-and-simulation-study-identifying-gender-differences-of-daily-olanzapine-dose-and-dopamine-d2-receptor-occupancy
#19
Andy R Eugene, Jolanta Masiak
BACKGROUND: Gender differences in treatment response rates for patients treated with antipsychotics are known. However, the literature lacks a pharmacodynamic model to allow for gender-based clinical trial simulations from modelling parameters for Olanzapine and dopamine D2 receptor occupancy. Thus, the primary aim of this analysis is to test and quantify the effect of gender on the pharmacodynamics of Olanzapine. METHODS: Population pharmacodynamic modelling was performed using non-linear mixed effects modelling in MONOLIX, while the Clinical Trial Simulations were performed using R for statistical programming...
May 9, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28479505/effects-of-monocrotophos-pesticide-on-cholinergic-and-dopaminergic-neurotransmitter-systems-during-early-development-in-the-sea-urchin-hemicentrotus-pulcherrimus
#20
Xiaona Zhang, Shuman Li, Cuicui Wang, Hua Tian, Wei Wang, Shaoguo Ru
During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae...
May 4, 2017: Toxicology and Applied Pharmacology
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