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Nmda receptor antagonist

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https://www.readbyqxmd.com/read/28924012/inhibition-of-il-1%C3%AE-signaling-normalizes-nmda-dependent-neurotransmission-and-reduces-seizure-susceptibility-in-a-mouse-model-of-creutzfeldt-jakob-disease
#1
Ilaria Bertani, Valentina Iori, Massimo Trusel, Mattia Maroso, Claudia Foray, Susanna Mantovani, Raffaella Tonini, Annamaria Vezzani, Roberto Chiesa
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic (EEG) abnormalities and seizures. Its neurophysiological bases are not known. To assess the potential involvement of N-methyl-D-aspartate receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knockout (KO) mice...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28918254/permissive-role-for-mglu1-metabotropic-glutamate-receptors-in-excitotoxic-retinal-degeneration
#2
Francesca Liberatore, Domenico Bucci, Giada Mascio, Michele Madonna, Paola Di Pietro, Martina Beneventano, Alda Maria Puliti, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, Maria Rosaria Romano
Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age- related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3 g/kg), which caused the death of >70% of Brn-3a(+) RGCs...
September 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28917975/the-memory-ameliorating-effects-of-dhp1402-an-herbal-mixture-on-cholinergic-blockade-induced-cognitive-dysfunction-in-mice
#3
Haneul Kim, Hyung Eun Lee, In Ho Jung, Se Jin Jeon, Jiabao Zhang, Yubeen Kwon, Dae Sik Jang, Jong Hoon Ryu
ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (rhamnaceae) and Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook.f. ex Trautv. (campanulaceae), compositions of DHP1402, have long been used for treating anti-dementia or hypomnesia as folk medicine. AIM OF THE STUDY: It has been reported that Z. jujuba var. spinosa and C. lanceolata are effective on cognitive function with different mechanism of action. Therefore, in the present study, we evaluated the synergistic effects of Ziziphus jujuba var...
September 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28917837/memantine-inhibits-%C3%AE-amyloid-aggregation-and-disassembles-preformed-%C3%AE-amyloid-aggregates
#4
Kaori Ito, Mitsuhiro Makino, Keiko Okado, Taisuke Tomita
Memantine, an uncompetitive glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, is widely used as a medication for the treatment of Alzheimer's disease (AD). We previously reported that chronic treatment of AD with memantine reduces the amount of insoluble β-amyloid (Aβ) and soluble Aβ oligomers in animal models of AD. The mechanisms by which memantine reduces Aβ levels in the brain were evaluated by determining the effect of memantine on Aβ aggregation using thioflavin T and transmission electron microscopy...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916627/interactions-between-medial-prefrontal-cortex-and-dorsomedial-striatum-are-necessary-for-odor-span-capacity-in-rats-role-of-glun2b-containing-nmda-receptors
#5
Don A Davies, Quentin Greba, Jantz C Selk, Jillian K Catton, Landon D Baillie, Sean J Mulligan, John G Howland
Working memory is involved in the maintenance and manipulation of information essential for complex cognition. While the neural substrates underlying working memory capacity have been studied in humans, considerably less is known about the circuitry mediating working memory capacity in rodents. Therefore, the present experiments tested the involvement of medial prefrontal cortex (mPFC) and dorsal striatum (STR) in the odor span task (OST), a task proposed to assay working memory capacity in rodents. Initially, Long Evans rats were trained to dig in scented sand for food following a serial delayed nonmatching-to-sample rule...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916251/mk-801-but-not-naloxone-attenuates-high-dose-dextromethorphan-induced-convulsive-behavior-possible-involvement-of-the-glun2b-receptor
#6
Hai-Quyen Tran, Yoon Hee Chung, Eun-Joo Shin, The-Vinh Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity...
September 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28916137/oxytocin-induces-penile-erection-and-yawning-when-injected-into-the-bed-nucleus-of-the-stria-terminalis-involvement-of-glutamic-acid-dopamine-and-nitric-oxide
#7
Fabrizio Sanna, Jessica Bratzu, Antonio Argiolas, Maria Rosaria Melis
Oxytocin (5-100ng), but not Arg(8)-vasopressin (100ng), injected unilaterally into the bed nucleus of the stria terminalis (BNST) induces penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished not only by the oxytocin receptor antagonist d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (1μg), but also by (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin...
September 12, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28912687/alterations-in-properties-of-glutamatergic-transmission-in-the-temporal-cortex-and-hippocampus-following-pilocarpine-induced-acute-seizures-in-wistar-rats
#8
Dmitry V Amakhin, Sergey L Malkin, Julia L Ergina, Kirill A Kryukov, Ekaterina A Veniaminova, Olga E Zubareva, Aleksey V Zaitsev
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in humans, and is often developed after an initial precipitating brain injury. This form of epilepsy is frequently resistant to pharmacological treatment; therefore, the prevention of TLE is the prospective approach to TLE therapy. The lithium-pilocarpine model in rats replicates some of the main features of TLE in human, including the pathogenic mechanisms of cell damage and epileptogenesis after a primary brain injury. In the present study, we investigated changes in the properties of glutamatergic transmission during the first 3 days after pilocarpine-induced acute seizures in Wistar rats (PILO-rats)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28912557/a-nmda-receptor-calcium-influx-assay-sensitive-to-stimulation-by-glutamate-and-glycine-d-serine
#9
Hongqiu Guo, L Miguel Camargo, Fred Yeboah, Mary Ellen Digan, Honglin Niu, Yue Pan, Stephan Reiling, Gilberto Soler-Llavina, Wilhelm A Weihofen, Hao-Ran Wang, Y Gopi Shanker, Travis Stams, Anke Bill
N-methyl-D-aspartate-receptors (NMDARs) are ionotropic glutamate receptors that function in synaptic transmission, plasticity and cognition. Malfunction of NMDARs has been implicated in a variety of nervous system disorders, making them attractive therapeutic targets. Overexpression of functional NMDAR in non-neuronal cells results in cell death by excitotoxicity, hindering the development of cell-based assays for NMDAR drug discovery. Here we report a plate-based, high-throughput approach to study NMDAR function...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910980/neuroprotective-effect-of-deferoxamine-on-n-methyl-d-aspartate-induced-excitotoxicity-in-rgc-5-cells
#10
Ying Tian, Ye He, Weitao Song, Endong Zhang, Xiaobo Xia
Many N-methyl-d-aspartate (NMDA) receptor antagonists have been used to treat neurodegenerative diseases induced by glutamate excitotoxicity in clinics. However, the universality of the glutamic acid neurotransmitter system makes the glutamic acid receptor blockers inefficient and unsafe. Thus, regulating the downstream signaling pathway in the excitotoxicity of glutamic acid may be a more effective and safer way to antagonize the glutamic acid receptor. In this study, we investigated the effect of deferoxamine (DFO), an iron chelator, on the NMDA-induced excitotoxicity...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28899728/maslinic-acid-ameliorates-nmda-receptor-blockade-induced-schizophrenia-like-behaviors-in-mice
#11
Se Jin Jeon, Eunji Kim, Jin Su Lee, Hee Kyong Oh, Jiabao Zhang, Yubeen Kwon, Dae Sik Jang, Jong Hoon Ryu
Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28886144/pharmacological-characterisation-of-s-47445-a-novel-positive-allosteric-modulator-of-ampa-receptors
#12
Sylvie Bretin, Caroline Louis, Laure Seguin, Stéphanie Wagner, Jean-Yves Thomas, Sylvie Challal, Nathalie Rogez, Karine Albinet, Fabrice Iop, Nadège Villain, Sonia Bertrand, Ali Krazem, Daniel Bérachochéa, Stéphanie Billiald, Charles Tordjman, Alex Cordi, Daniel Bertrand, Pierre Lestage, Laurence Danober
S 47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPA-PAM). S 47445 enhanced glutamate's action at AMPA receptors on human and rat receptors and was inactive at NMDA and kainate receptors. Potentiation did not differ among the different AMPA receptors subtypes (GluA1/2/4 flip and flop variants) (EC50 between 2.5-5.4 μM), except a higher EC50 value for GluA4 flop (0.7 μM) and a greater amount of potentiation on GluA1 flop. A low concentration of S 47445 (0...
2017: PloS One
https://www.readbyqxmd.com/read/28882191/effects-of-sustained-i-c-v-infusion-of-lupus-csf-and-autoantibodies-on-behavioral-phenotype-and-neuronal-calcium-signaling
#13
Minesh Kapadia, Dunja Bijelić, Hui Zhao, Donglai Ma, Ljudmila Stojanovich, Milena Milošević, Pavle Andjus, Boris Šakić
Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease that is often accompanied by brain atrophy and diverse neuropsychiatric manifestations of unknown origin. More recently, it was observed that cerebrospinal fluid (CSF) from patients and lupus-prone mice can be neurotoxic and that acute administration of specific brain-reactive autoantibodies (BRAs) can induce deficits in isolated behavioral tasks. Given the chronic and complex nature of CNS SLE, the current study examines broad behavioral performance and neuronal Ca(2+) signaling in mice receiving a sustained infusion of cerebrospinal fluid (CSF) from CNS SLE patients and putative BRAs (anti-NR2A, anti-ribosomal P, and anti-α-tubulin)...
September 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28877137/a-systematic-review-of-nmda-receptor-antagonists-for-treatment-of-neuropathic-pain-in-clinical-practice
#14
Rohit Aiyer, Neel Mehta, Semih Gungor, Amitabh Gulati
OBJECTIVE: To investigate the efficacy of N-methyl-D-aspartate receptor (NMDA) receptor antagonists for neuropathic pain and review literature to determine if specific pharmacologic agents provide adequate neuropathic pain relief. METHODS: Literature was reviewed on PubMed using a variety of key words for 8 NMDA receptor antagonists. These key words include: "Ketamine and Neuropathy", "Ketamine and Neuropathic Pain", "Methadone and Neuropathy", "Methadone and Neuropathic Pain", "Memantine and Neuropathic pain", "Memantine and Neuropathy", "Amantadine and Neuropathic Pain", "Amantadine and Neuropathy", "Dextromethorphan and Neuropathic Pain", "Dextromethorphan and Neuropathy", "Carbamazepine and Neuropathic Pain", "Carbamazepine and Neuropathy", "Valproic Acid and Neuropathy", "Valproic Acid and Neuropathic Pain", "Phenytoin and Neuropathy" and "Phenytoin and Neuropathic Pain"...
September 1, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28872835/revisiting-the-quinoxalinedione-scaffold-in-the-construction-of-new-ligands-for-the-ionotropic-glutamate-receptors
#15
Charles S Demmer, David Rombach, Na Liu, Birgitte Nielsen, Darryl S Pickering, Lennart Bunch
More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work, we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity among the AMPA, NMDA, and KA receptors, and to some extent also obtain full receptor subtype selectivity...
September 5, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28872832/chemically-modified-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-ampa-receptor-rna-aptamers-designed-for-in-vivo-use
#16
Zhen Huang, Wei Wen, Andrew Wu, Li Niu
Glutamate ion channels have three subtypes, that is, α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA), kainate, and N-methyl-d-aspartate (NMDA) receptors. Excessive activity of these receptor subtypes either individually or collectively is involved in various neurological disorders. RNA aptamers as antagonists of these receptors are potential therapeutics. For developing aptamer therapeutics, the RNA aptamers must be chemically modified to become ribonuclease-resistant or stable in biological fluids. Using systematic evolution of ligands by exponential enrichment (SELEX) and a chemically modified library, prepared enzymatically (i...
September 5, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28870570/effects-of-naftopidil-on-inhibitory-transmission-in-substantia-gelatinosa-neurons-of-the-rat-spinal-dorsal-horn-in-vitro
#17
Daisuke Uta, Du-Jie Xie, Tsuyoshi Hattori, Ken-Ichi Kasahara, Megumu Yoshimura
OBJECTIVE: Naftopidil is used clinically for the treatment of voiding disorders in benign prostatic hyperplasia. Previous in vivo experiments in which naftopidil was applied intrathecally abolished rhythmic bladder contraction, suggesting that naftopidil might inhibit a voiding reflex through interaction with spinal dorsal horn neurons. Here we aimed to clarify the mechanism of action of naftopidil on dorsal horn neurons. METHODS: Whole-cell patch-clamp recordings were performed using substantia gelatinosa neurons of adult rat spinal cord slices...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28867363/methoxetamine-produces-rapid-and-sustained-antidepressant-effects-probably-via-glutamatergic-and-serotonergic-mechanisms
#18
Chrislean Jun Botanas, June Bryan de la Peña, Raly James Custodio, Irene Joy Dela Peña, Mikyung Kim, Taeseon Woo, Hee Jin Kim, Hye In Kim, Min Chang Cho, Yong Sup Lee, Jae Hoon Cheong
Depression afflicts around 16% of the world's population, making it one of the leading causes of disease burden worldwide. Despite a number of antidepressants available today, the delayed onset time and low remission rate of these treatments are still a major challenge. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown to produce rapid and sustained antidepressant effects and has paved the way for a new generation of glutamate-based antidepressants. Methoxetamine (MXE) is a ketamine analogue that acts as an NMDA receptor antagonist and a serotonin reuptake inhibitor...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28866050/orexin-receptors-mediate-long-term-depression-of-excitatory-synaptic-transmission-in-the-spinal-cord-dorsal-horn
#19
Ki Bum Park, Haein Weon
Neuropeptides orexin-A and -B are related to the regulation of sleep/wakefulness and feeding behaviors. Recently, the peptides have also been shown to yield antinociceptive effects in various pain models. However, it is not clear whether orexins are involved in forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), the increase and the decrease of synaptic efficacy, respectively. In the present study, we examined whether orexin receptor type 1 (OX1) and 2 (OX2) are involved in the induction or maintenance of LTD of excitatory synaptic transmission using transverse spinal cord slices of young rats...
September 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28864281/interaction-of-brain-derived-neurotrophic-factor-val66met-genotype-and-history-of-stress-in-regulation-of-prepulse-inhibition-in-mice
#20
Maarten van den Buuse, John Juan Wen Lee, Emily J Jaehne
The Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism results in reduced activity-dependent BDNF release and has been implicated in schizophrenia. However, effects of the polymorphism on functional dopaminergic and N-methyl-d-aspartate (NMDA) receptor-associated activity remain unclear. We used prepulse inhibition, a measure of sensorimotor gating which is disrupted in schizophrenia, and assessed the effects of acute treatment with the dopamine receptor agonist, apomorphine (APO), and the NMDA receptor antagonist, MK-801...
August 29, 2017: Schizophrenia Research
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