keyword
MENU ▼
Read by QxMD icon Read
search

NMDA antagonist

keyword
https://www.readbyqxmd.com/read/28749574/design-synthesis-pharmacological-evaluation-and-docking-studies-of-glun2b-selective-nmda-receptor-antagonists-with-a-benzo-7-annulen-7-amine-scaffold
#1
Sandeep Gawaskar, Louisa Temme, Julian A Schreiber, Dirk Schepmann, Alessandro Bonifazi, Dina Robaa, Wolfgang Sippl, Nathalie Strutz-Seebohm, Guiscard Seebohm, Bernhard Wünsch
Antagonists that selectively target GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptors are of major interest for the treatment of various neurological disorders. In this study, relationships between variously substituted benzo[7]annulen-7-amines and their GluN2B affinity were investigated. 2-Nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one (8) represents the central building block for the introduction of various substituents at the 2-position and various 7-amino moieties. N-(3-Phenylpropyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amines with a 2-NO2 (7 c), 2-Cl (15 c), or 2-OBn group (22 c) show very high GluN2B affinity (Ki =1...
July 27, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28748171/effect-of-linalool-on-the-acquisition-and-reinstatement-of-morphine-induced-conditioned-place-preference-in-mice
#2
Narjes Pourtaqi, Mohsen Imenshahidi, Bibi Marjan Razavi, Hossein Hosseinzadeh
OBJECTIVE: The effect of linalool, a terpene alcohol found in many plants, which inhibits NMDA receptors, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) was evaluated in mice. MATERIAL AND METHODS: The effects of different doses of linalool (12.5, 25 and 50 mg/kg, i.p.), memantine (20 mg/kg, an NMDA receptor antagonist) and saline, in CPP induced by 40 mg/kg of morphine were investigated in mice. In another experiment, a single injection of morphine (10 mg/kg) reinstated the place reference following extinction of a place preference induced by morphine (40 mg/kg)...
May 2017: Avicenna Journal of Phytomedicine
https://www.readbyqxmd.com/read/28747405/nmda-receptor-dependent-presynaptic-inhibition-at-the-calyx-of-held-synapse-of-rat-pups
#3
Tomoko Oshima-Takago, Hideki Takago
N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation modulates transmitter release. However, the regulatory mechanisms of NMDAR-dependent synaptic transmission remain largely unknown. In the present study, we demonstrated that activation of NMDARs in a nerve terminal at a central glutamatergic synapse inhibits presynaptic Ca(2+) currents (ICa) in a GluN2C/2D subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic currents...
July 2017: Open Biology
https://www.readbyqxmd.com/read/28742157/angiotensin-ii-system-in-the-nucleus-tractus-solitarii-contributes-to-autonomic-dysreflexia-in-rats-with-spinal-cord-injury
#4
Kai Wang, Shaoxia Duan, Xueping Wen, Weizhong Wang, Shangping Fang, Dunyi Qi, Xiang Huan, Liwei Wang, Zhenzhou He
BACKGROUND: Autonomic dysreflexia (AD) is a potentially life-threating complication after spinal cord injury (SCI), characterized by episodic hypertension induced by colon or bladder distension. The objective of this study was to determine the role of impaired baroreflex regulation by the nucleus tractus solitarii(NTS) in the occurrence of AD in a rat model. METHODS: T4 spinal cord transection animal model was used in this study, which included 40 Male rats Colorectal distension (CD) was performed to assess AD and compare the changes of BP, HR, and BRS, six weeks after operation...
2017: PloS One
https://www.readbyqxmd.com/read/28739134/nmda-receptor-modulation-by-dextromethorphan-and-acute-stress-selectively-alters-electroencephalographic-indicators-of-partial-report-processing
#5
Lisa J Weckesser, Sören Enge, Philipp Riedel, Clemens Kirschbaum, Robert Miller
Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions...
July 21, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28737885/classics-in-chemical-neuroscience-memantine
#6
Shahrina Alam, Kaelyn Skye Lingenfelter, Aaron M Bender, Craig W Lindsley
Memantine was the first breakthrough medication for the treatment of moderate to severe Alzheimer's disease (AD) patients, and represents a fundamentally new mechanism of action (moderate-affinity, uncompetitive, voltage-dependent, N-methyl-D-aspartate (NMDA) receptor antagonist that exhibits fast on/off kinetics) to modulate glutamatergic dysfunction. Since its approval by the FDA in 2003, memantine, alone, and in combination with donepezil, has improved patient outcomes in terms of cognition, behavioral disturbances, daily functioning and delaying time to institutionalization...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28736332/5-hydroxytryptamine-2a-receptors-of-the-dorsal-raphe-nucleus-mediate-panic-like-behaviours-and-fear-induced-antinociception-elicited-by-neuronal-activation-in-the-central-nucleus-of-the-inferior-colliculus
#7
Raimundo da Silva Soares, Luiz Luciano Falconi-Sobrinho, Tayllon Dos Anjos-Garcia, Norberto Cysne Coimbra
It has been established that chemical stimulation of the inferior colliculus (IC) of laboratory animals evokes fear-related defensive responses, which are considered panic attack-like behaviours. In addition, there is evidence that defensive reactions provoked by chemical stimulation of midbrain tectum neurons may induce an antinociceptive response. Morphologically, the IC receives projections from other mesencephalic structures, such as the dorsal raphe nucleus (DRN), a region rich in serotonergic neurons that play a critical role in the control of defensive behaviours...
July 20, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28733356/steady-state-free-ca2-in-astrocytes-is-decreased-by-experience-and-impacts-arteriole-tone
#8
Eslam M F Mehina, Ciaran Murphy-Royal, Grant R Gordon
Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca2+ activity. However, whether resting astrocyte Ca2+ can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca2+ imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca2+ in the soma and endfeet. The drop in intracellular Ca2+ was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca2+ stores and nitric oxide...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28731926/history-of-anaesthesia-the-ketamine-story-past-present-and-future
#9
Georges Mion
: Ketamine's history begins in the 1950s in Detroit, Michigan, at Parke-Davis Laboratories. On 26 March 1956, Harold V. Maddox synthesised phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl did not cause depression of cardiovascular and respiratory functions, but elicited severe excitation with a very prolonged postoperative recovery. Because of its psychedelic effects, it became a street drug under the name of 'angel dust' and was placed on schedule II of Federal Controlled Substance Act (CSA) in 1978...
July 20, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28731405/pro-death-nmda-receptor-signaling-is-promoted-by-the-glun2b-c-terminus-independently-of-dapk1
#10
Jamie McQueen, Tomas J Ryan, Sean McKay, Katie Fm Marwick, Paul E Baxter, Sarah M Carpanini, Thomas M Wishart, Thomas H Gillingwater, Jean C Manson, David Ja Wyllie, Seth Gn Grant, Barry McColl, Noboru Komiyama, Giles E Hardingham
Aberrant NMDA receptor (NMDAR) activity contributes to several neurological disorders, but direct antagonism is poorly tolerated therapeutically. The GluN2B cytoplasmic C-terminal domain (CTD) represents an alternative therapeutic target since it potentiates excitotoxic signaling. The key GluN2B CTD-centred event in excitotoxicity is proposed to involve its phosphorylation at Ser-1303 by DAPK1, that is blocked by a neuroprotective cell-permeable peptide mimetic of the region. Contrary to this model, we find that excitotoxicity can proceed without increased Ser-1303 phosphorylation, and is unaffected by DAPK1 deficiency in vitro or following ischemia in vivo...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28730337/memantine-can-reduce-ethanol-induced-caspase-3-activity-and-apoptosis-in-h4-cells-by-decreasing-intracellular-calcium
#11
Xiaolong Wang, Jiajun Chen, Hongbo Wang, Hao Yu, Changliang Wang, Jiabin You, Pengfei Wang, Chunmei Feng, Guohui Xu, Xu Wu, Rui Zhao, Guohua Zhang
Caspase-3 activation and apoptosis are associated with various neurodegenerative disorders. Calcium activation is an important factor in promoting apoptosis. We, therefore, assessed the role of intracellular calcium in ethanol-induced activation of caspase-3 in H4 human neuroglioma cells and the protective effect of the NMDA receptor antagonist, memantine, on ethanol-induced apoptosis in H4 cells. H4 cells were treated with 100 mM EtOH (in culture medium) for 2 days. For interaction studies, cells were treated with memantine (4 μM), EDTA (1 mM), or BAPTA-AM (10 μM) before treatment with EtOH...
July 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28726541/characterization-of-postsynaptic-calcium-signals-in-the-pyramidal-neurons-of-anterior-cingulate-cortex
#12
Xu-Hui Li, Qian Song, Tao Chen, Min Zhuo
Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28713246/differential-contribution-of-ca-2-dependent-mechanisms-to-hyperexcitability-in-layer-v-neurons-of-the-medial-entorhinal-cortex
#13
Eric C Lin, Crescent L Combe, Sonia Gasparini
Temporal lobe epilepsy is characterized by recurrent seizures in one or both temporal lobes of the brain; some in vitro models show that epileptiform discharges initiate in entorhinal layer V neurons and then spread into other areas of the temporal lobe. We previously found that, in the presence of GABAA receptor antagonists, stimulation of afferent fibers, terminating both at proximal and distal dendritic locations, initiated hyperexcitable bursts in layer V medial entorhinal neurons. We investigated the differential contribution of Ca(2+)-dependent mechanisms to the plateaus underlying these bursts at proximal and distal synapses...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#14
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708400/contribution-of-mate1-to-renal-secretion-of-the-nmda-receptor-antagonist-memantine
#15
Fabian Müller, Dietmar Weitz, Volker Derdau, Martin Sandvoss, Katharina Mertsch, Jörg König, Martin F Fromm
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport...
July 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28704758/deconstruction-reconstruction-approach-to-analyze-the-essential-structural-elements-of-tetrahydro-3-benzazepine-based-antagonists-of-glun2b-subunit-containing-nmda-receptors
#16
Sougata Dey, Louisa Temme, Julian A Schreiber, Dirk Schepmann, Bastian Frehland, Kirstin Lehmkuhl, Nathalie Strutz-Seebohm, Guiscard Seebohm, Bernhard Wünsch
The role of the phenolic and benzylic OH moieties for the interaction of tetrahydro-3-benzazepine-1,7-diol 3d with GluN2B subunit containing NMDA receptors was analyzed by their stepwise removal. Elimination of trifluormethanesulfinate from 10 and 13 represent the key steps in the synthesis. Removal of phenolic OH moiety led to 5-fold reduced GluN2B affinity of 4d compared with 3d. Additional removal of the benzylic OH moiety (5d) resulted in further reduced GluN2B affinity but increased σ1 and σ2 affinities...
July 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28695335/glutamatergic-system-and-mtor-signaling-pathway-participate-in-the-antidepressant-like-effect-of-inosine-in-the-tail-suspension-test
#17
Filipe Marques Gonçalves, Vivian Binder Neis, Débora Kurrle Rieger, Tanara V Peres, Mark William Lopes, Isabella A Heinrich, Ana Paula Costa, Ana Lúcia S Rodrigues, Manuella P Kaster, Rodrigo Bainy Leal
Glutamatergic system and mTOR signaling pathway have been proposed to be important targets for pharmacological treatment of major depressive disorder. Previous studies have shown that inosine, an endogenous purine, is able to exert a remarkable antidepressant-like effect in mice. Nevertheless, the role of glutamatergic system and mTOR in this effect was not previously determined. This study was designed to investigate the possible modulation of NMDA receptors (NMDAR), AMPA receptors (AMPAR) and mTOR complex 1 (mTORC1) signaling pathway in the inosine anti-immobility effect in the tail suspension test (TST) in mice...
July 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28694097/behavioural-pharmacology-of-the-%C3%AE-5-gabaa-receptor-antagonist-s44819-enhancement-and-remediation-of-cognitive-performance-in-preclinical-models
#18
István Gacsályi, Krisztina Móricz, Gábor Gigler, János Wellmann, Katalin Nagy, István Ling, József Barkóczy, József Haller, Jeremy J Lambert, Gábor Szénási, Michael Spedding, Ferenc A Antoni
Previous work has shown that S44819 is a novel GABAA receptor (GABAAR) antagonist, which is selective for extrasynaptic GABAARs incorporating the α5 subunit (α5-GABAARs). The present study reports on the preclinical neuropsychopharmacological profile of S44819. Significantly, no sedative or pro-convulsive side effects of S44819 were found at doses up to 30 mg/kg i.p. Object recognition (OR) memory in intact mice was enhanced by S44819 (0.3 mg/kg p.o.) given before the acquisition trial. Mice treated with phencyclidine for two weeks and tested six days after the cessation of treatment failed to show OR memory...
July 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28691718/additive-and-antagonistic-antinociceptive-interactions-between-magnesium-sulfate-and-ketamine-in-the-rat-formalin-test
#19
Katarina Savić Vujović, Sonja Vučković, Dolika Vasović, Branislava Medić, Nick Knežević, Milica Prostran
Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Animals were injected with 100 μL of 2.5% formalin to the plantar surface of the right hind paw. Data were recorded as the total time spent in pain-related behavior after the injection of formalin or vehicle (0...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28688912/inhibition-of-the-kynurenine-pathway-protects-against-reactive-microglial-associated-reductions-in-the-complexity-of-primary-cortical-neurons
#20
Katherine O'Farrell, Eimear Fagan, Thomas J Connor, Andrew Harkin
Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP...
July 5, 2017: European Journal of Pharmacology
keyword
keyword
69628
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"