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Nmda receptor antagonist

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https://www.readbyqxmd.com/read/27916716/effects-of-a-non-competitive-n-methyl-d-aspartate-nmda-antagonist-tiletamine-in-adult-zebrafish
#1
Tatiana O Kolesnikova, Sergey L Khatsko, Vadim A Shevyrin, Yuri Yu Morzherin, Allan V Kalueff
Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species...
December 1, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27910870/antinociceptive-profile-of-levo-tetrahydropalmatine-in-acute-and-chronic-pain-mice-models-role-of-spinal-sigma-1-receptor
#2
Dong-Wook Kang, Ji-Young Moon, Jae-Gyun Choi, Suk-Yun Kang, Yeonhee Ryu, Jin Bong Park, Jang-Hern Lee, Hyun-Woo Kim
We have recently reported that repeated systemic treatments of extract from Corydalis yanhusuo alleviate neuropathic pain and levo-tetrahydropalmatine (l-THP) is one of active components from Corydalis. We designed this study to investigate antinociceptive effect of l-THP in acute and chronic pain models and related mechanism within the spinal cord. We found that intraperitoneal pretreatment with l-THP significantly inhibited the second phase of formalin-induced pain behavior. In addition, intrathecal as well as intraperitoneal pretreatment with l-THP reduced the mechanical allodynia (MA) induced by direct activation of sigma-1 receptor (Sig-1)...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908707/the-role-of-nmda-receptor-and-nitric-oxide-cyclic-guanosine-monophosphate-pathway-in-the-antidepressant-like-effect-of-dextromethorphan-in-mice-forced-swimming-test-and-tail-suspension-test
#3
Ehsan Sakhaee, Sattar Ostadhadi, Muhammad Imran Khan, Farbod Yousefi, Abbas Norouzi-Javidan, Reyhaneh Akbarian, Mohsen Chamanara, Samira Zolfaghari, Ahmad-Reza Dehpour
Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling...
November 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27907838/fear-memory-in-a-neurodevelopmental-model-of-schizophrenia-based-on-the-postnatal-blockade-of-nmda-receptors
#4
Joachim Latusz, Aleksandra Radaszkiewicz, Ewelina Bator, Krzysztof Wędzony, Marzena Maćkowiak
BACKGROUND: Epidemiological data have indicated that memory impairment is observed during adolescence in groups at high risk for schizophrenia and might precede the appearance of schizophrenia symptoms in adulthood. METHODS: In the present study, we used a neurodevelopmental model of schizophrenia based on the postnatal blockade of N-methyl-d-aspartate (NMDA) receptors in rats to investigate fear memory in adolescence and adulthood. The rats were treated with increasing doses of CGP 37849 (CGP), a competitive antagonist of the NMDA receptor (1...
October 17, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27900470/influence-of-the-selective-antagonist-of-the-nr2b-subunit-of-the-nmda-receptor-traxoprodil-on-the-antidepressant-like-activity-of-desipramine-paroxetine-milnacipran-and-bupropion-in-mice
#5
Weronika Stasiuk, Aleksandra Szopa, Anna Serefko, Elżbieta Wyska, Katarzyna Świąder, Jarosław Dudka, Piotr Wlaź, Ewa Poleszak
Pre-clinical and clinical studies indicated that a blockade of the NMDA receptor complex creates new opportunities for the treatment of affective disorders, including depression. The aim of the present study was to assess the influence of traxoprodil (10 mg/kg) on the activity of desipramine (10 mg/kg), paroxetine (0.5 mg/kg), milnacipran (1.25 mg/kg), and bupropion (10 mg/kg), each at sub-therapeutic doses. Moreover, brain levels of traxoprodil and tested agents were determined using HPLC. The obtained results were used to ascertain the nature of occurring interaction between traxoprodil and studied antidepressants...
November 29, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27896651/postnatal-administration-of-dizocilpine-inhibits-neuronal-excitability-in-pfc-and-induces-social-deficits-detected-by-miceprofiler
#6
Dexiao Zhu, Hui Wang, Jintao Wu, Qian Wang, Ling Xu, Yue Zhao, Kunkun Pang, Qingqing Shi, Wenbo Zhao, Jing Zhang, Jinhao Sun
Schizophrenia is a devastating mental disease with social deficit as its core component of negative symptoms, which could be induced in rodents by dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly expressed during the postnatal period. However, less attention has been paid to the effects of postnatal MK-801 administration on social interaction. In this study, we evaluated the effects of postnatal administration of MK-801 on social interaction and explored the possible mechanisms...
November 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27894877/relief-learning-requires-a-coincident-activation-of-dopamine-d1-and-nmda-receptors-within-the-nucleus-accumbens
#7
Jorge R Bergado Acosta, Evelyn Kahl, Georgios Kogias, Taygun C Uzuneser, Markus Fendt
Relief learning is the association of a stimulus with the offset of an aversive event. Later, the now conditioned relief stimulus induces appetitive-like behavioral changes. We previously demonstrated that the NMDA receptors within the nucleus accumbens (NAC) are involved in relief learning. The NAC is also important for reward learning and it has been shown that reward learning is mediated by an interaction of accumbal dopamine and NMDA glutamate receptors. Since conditioned relief has reward-like properties, we hypothesized that (a) acquisition of relief learning requires the activation of dopamine D1 receptors in the NAC, and (b) if D1 receptors are involved in this process as expected, a concurrent dopamine D1 and NMDA receptor activation may mediate this learning...
November 26, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889488/enhanced-ltp-in-aged-rats-detrimental-or-compensatory
#8
Júlia Pinho, Ruben Vale, Vânia L Batalha, Ana Rita Costenla, Raquel Dias, Diogo Rombo, Ana M Sebastião, Alexandre de Mendonça, Maria José Diógenes
Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated. The results show that memantine significantly decreases the larger LTP magnitude recorded in hippocampal slices from aged rats without compromising LTP recorded in slices from young and adult animals...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27889096/novel-functional-properties-of-drosophila-cns-glutamate-receptors
#9
Yan Li, Poorva Dharkar, Tae-Hee Han, Mihaela Serpe, Chi-Hon Lee, Mark L Mayer
Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27878487/paradoxical-effect-of-nmda-receptor-blockade-in-chicks-on-learning-and-memory-in-passive-avoidance-model
#10
A A Tiunova, N V Komissarova, D V Bezryadnov, K V Anokhin
Activity of NMDA receptors is a prerequisite for numerous but not all forms of neuronal plasticity and learning. The present study examined the role of NMDA receptors in standard, weak, and repeated passive avoidance training in young chicks. Injection of MK-801, an antagonist of NMDA receptor, prior to strong training episode impaired subsequent memory recall. Moreover, repeated training did not restore the lost memory. In the double weak training protocol, the impairing effect of MK-801 was observed only when it was injected prior to the second but not to the first training episode...
November 22, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27875784/anticonvulsant-effect-of-dextrometrophan-on-pentylenetetrazole-induced-seizures-in-mice-involvement-of-nitric-oxide-and-n-methyl-d-aspartate-receptors
#11
Gholamreza Mohseni, Sattar Ostadhadi, Reyhaneh Akbarian, Mohsen Chamanara, Abbas Norouzi-Javidan, Ahmad-Reza Dehpour
Dextrometrophan (DM), widely used as an antitussive, has recently generated interest as an anticonvulsant drug. Some effects of dextrometrophan are associated with alterations in several pathways, such as inhibition of nitric oxide synthase (NOS) enzyme and N-methyl d-aspartate (NMDA) receptors. In this study, we aimed to investigate the anticonvulsant effect of acute administration of dextrometrophan on pentylenetetrazole (PTZ)-induced seizures and the probable involvement of the nitric oxide (NO) pathway and NMDA receptors in this effect...
November 19, 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27872695/reduction-of-the-morphine-maintenance-by-blockade-of-the-nmda-receptors-during-extinction-period-in-conditioned-place-preference-paradigm-of-rats
#12
Ali Siahposht-Khachaki, Zahra Fatahi, Abbas Haghparast
INTRODUCTION: Activation of N-methyl-d-aspartate (NMDA) glutamate receptors in the nucleus accumbens is a component of drug-induced reward mechanism. In addition, NMDA receptors play a major role in brain reward system and activation of these receptors can change firing pattern of dopamine neurons. Blockade of glutamatergic neurotransmission reduces the expression of conditioned place preference (CPP) induced by morphine. Therefore, in this study, by using an NMDA receptor antagonist, DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5), the role of NMDA receptors on the maintenance and reinstatement of morphine-CPP was investigated...
October 2016: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/27871866/effects-of-the-glun2b-nmda-receptor-antagonist-ro-25-6981-on-two-types-of-behavioral-flexibility-in-rats
#13
Emma Clark, Kristen Antoniak, Alyssandra Feniquito, Hans C Dringenberg
Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning and behavioral flexibility in rodents. Here, we examined the effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal learning and set-shifting (spatial vs. motor strategy). To examine spatial reversal learning, rats were trained to swim to a hidden platform in a water maze over four days. On the following day, the platform was moved to a new location in the maze...
November 18, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27867308/effect-of-n-methyl-d-aspartate-receptor-antagonist-dextromethorphan-on-opioid-analgesia-in-pediatric-intensive-care-unit
#14
Mohammed Naeem, Hala Al Alem, Ali Al Shehri, Majed Al-Jeraisy
Objective. Pain control is an essential goal in the management of critical children. Narcotics are the mainstay for pain control. Patients frequently need escalating doses of narcotics. In such cases an adjunctive therapy may be beneficial. Dextromethorphan (DM) is NMDA receptor antagonist and may prevent tolerance to narcotics; however, its definitive role is still unclear. We sought whether dextromethorphan addition could decrease the requirements of fentanyl to control pain in critical children. Design. Double-blind, randomized control trial (RCT)...
2016: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/27867000/neuromodulatory-effects-of-the-dorsal-hippocampal-endocannabinoid-system-in-dextromethorphan-morphine-induced-amnesia
#15
Zahra Ghasemzadeh, Ameneh Rezayof
Dextromethorphan which is an active ingredient in many cough medicines has been previously shown to potentiate amnesic effect of morphine in rats. However, the effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, in combination with morphine on hippocampus-based long term memory has not been well characterized. The aim of the present study was to assess the possible role of endocannabinoid system of the dorsal hippocampus in dextromethorphan /morphine-induced amnesia...
November 17, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27865983/transdermal-therapeutic-systems-for-memantine-delivery-comparison-of-passive-and-iontophoretic-transport
#16
S Del Río-Sancho, C E Serna-Jiménez, M Sebastián-Morelló, M A Calatayud-Pascual, C Balaguer-Fernández, A Femenía-Font, Y N Kalia, V Merino, A López-Castellano
Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin...
November 16, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27865910/multi-target-directed-therapeutic-potential-of-7-methoxytacrine-adamantylamine-heterodimers-in-the-alzheimer-s-disease-treatment
#17
Zuzana Gazova, Ondrej Soukup, Vendula Sepsova, Katarina Siposova, Lucie Drtinova, Petr Jost, Katarina Spilovska, Jan Korabecny, Eugenie Nepovimova, Diana Fedunova, Martin Horak, Martina Kaniakova, Ze-Jun Wang, Ayman K Hamouda, Kamil Kuca
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and currently there is no efficient treatment. The classic drug-design strategy based on the "one-molecule-one-target" paradigm was found to be ineffective in the case of multifactorial diseases like AD. A novel multi-target-directed ligand strategy based on the assumption that a single compound consisting of two or more distinct pharmacophores is able to hit multiple targets has been proposed as promising. Herein, we investigated 7-methoxytacrine - memantine heterodimers developed with respect to the multi-target-directed ligand theory...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27860425/centrally-mediated-ejaculatory-response-via-sympathetic-outflow-in-rats-role-of-n-methyl-d-aspartic-acid-receptors-in-paraventricular-nucleus
#18
J-D Xia, J Chen, H-J Sun, L-H Zhou, G-Q Zhu, Y Chen, Y-T Dai
Ejaculation is mediated by a spinal generator, which integrates inputs related to the sexual activity and coordinates sympathetic, parasympathetic, and motor outflow. Previous clinical studies indicate that primary premature ejaculation is related to the hyperactivity of the sympathetic nervous system. In this study, we explored the roles of N-methyl-D-aspartic acid (NMDA) receptors in paraventricular nucleus of the hypothalamus (PVN) on ejaculatory responses and its potential mechanism in the rats. We found that microinjection of 0...
November 16, 2016: Andrology
https://www.readbyqxmd.com/read/27859797/in-vitro-and-in-vivo-effects-of-a-novel-dimeric-inhibitor-of-psd-95-on-excitotoxicity-and-functional-recovery-after-experimental-traumatic-brain-injury
#19
Jens Bak Sommer, Anders Bach, Hana Malá, Kristian Strømgaard, Jesper Mogensen, Darryl Scott Pickering
PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel dimeric inhibitor of PSD-95, UCCB01-147, on histopathology and long-term cognitive outcome after controlled cortical impact (CCI) in rats. As excitotoxic cell death is thought to be a prominent part of the pathophysiology of TBI, we also investigated the neuroprotective effects of UCCB01-147 and related compounds on NMDA-induced cell death in cultured cortical neurons...
November 17, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27858086/interaction-between-nmda-and-cb2-function-in-the-dorsal-hippocampus-on-memory-consolidation-impairment-an-isobologram-analysis
#20
Mohammad Nasehi, Marziyeh Hajikhani, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
RATIONALE: Convincing evidence has supported the pivotal role of N-methyl-D-aspartate receptors (NMDARs) and CB2Rs in the regulation of learning and memory. OBJECTIVE: In this study, the role of hippocampal (CA1 region) CB2 receptors on aversive memory consolidation deficit induced by D-AP5, a NMDA receptor antagonist, was evaluated. METHODS: Adult male Wistar rats received cannula implants that bilaterally targeted the CA1 region. Long-term memory was examined using the step-through type of passive avoidance task...
November 17, 2016: Psychopharmacology
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