scholarly journals Effects of the novel NMDA receptor antagonist, CGP 39551, on field potentials and the induction and expression of LTP in the dentate gyrus in vivo

Synapse ◽  
1992 ◽  
Vol 11 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Stephen Maren ◽  
Michel Baudry ◽  
Richard F. Thompson
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
The Novel ◽  
Field Potentials ◽  
Cgp 39551

scholarly journals A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 284 ◽  
Author(s):  
Júlia Companys-Alemany ◽  
Andreea L. Turcu ◽  
Aina Bellver-Sanchis ◽  
Maria I Loza ◽  
José M. Brea ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Late Onset ◽  
B Cell Lymphoma ◽  
Nmda Receptor Antagonist ◽  
Mice Model ◽  
Object Recognition Test ◽  
Protein Levels ◽  
Preclinical Treatment

Alzheimer’s disease (AD) is the leading cause of dementia. Non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist memantine improved cognition and molecular alterations after preclinical treatment. Nevertheless, clinical results are discouraging. In vivo efficacy of the RL-208, a new NMDA receptor blocker described recently, with favourable pharmacokinetic properties was evaluated in Senescence accelerated mice prone 8 (SAMP8), a mice model of late-onset AD (LOAD). Oral administration of RL-208 improved cognitive performance assessed by using the three chamber test (TCT), novel object recognition test (NORT), and object location test (OLT). Consistent with behavioural results, RL-208 treated-mice groups significantly changed NMDAR2B phosphorylation state levels but not NMDAR2A. Calpain-1 and Caspase-3 activity was reduced, whereas B-cell lymphoma-2 (BCL-2) levels increased, indicating reduced apoptosis in RL-208 treated SAMP8. Superoxide Dismutase 1 (SOD1) and Glutathione Peroxidase 1 (GPX1), as well as a reduction of hydrogen peroxide (H2O2), was also determined in RL-208 mice. RL-208 treatment induced an increase in mature brain-derived neurotrophic factor (mBDNF), prevented Tropomyosin-related kinase B full-length (TrkB-FL) cleavage, increased protein levels of Synaptophysin (SYN) and Postsynaptic density protein 95 (PSD95). In whole, these results point out to an improvement in synaptic plasticity. Remarkably, RL-208 also decreased the protein levels of Cyclin-Dependent Kinase 5 (CDK5), as well as p25/p35 ratio, indicating a reduction in kinase activity of CDK5/p25 complex. Consequently, lower levels of hyperphosphorylated Tau (p-Tau) were found. In sum, these results demonstrate the neuroprotectant role of RL-208 through NMDAR blockade.

(352) In vivo activation of SK channels reduces the dose of NMDA receptor antagonist needed to produce antinociception

2015 ◽  
Vol 16 (4) ◽  
pp. S64
Author(s):  
L. Hipólito ◽  
A. Fakira ◽  
D. Cabañero ◽  
P. Anand ◽  
J. Gonzalez-Romero ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Sk Channels

scholarly journals Phosphorylation of extracellular-regulating kinase in NMDA receptor antagonist-induced newly generated neurons in the adult rat dentate gyrus

2003 ◽  
Vol 88 (3) ◽  
pp. 717-725 ◽  
Author(s):  
Noriko Okuyama ◽  
Norio Takagi ◽  
Takayuki Kawai ◽  
Keiko Miyake-Takagi ◽  
Satoshi Takeo
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Adult Rat

Characterization of 3-carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC-48981), a potent competitive (NMDA) receptor antagonist, in vitro and in vivo

1992 ◽  
Vol 135 (2) ◽  
pp. 149-152 ◽  
Author(s):  
Michael L. Vazquez ◽  
Danny J. Garland ◽  
Eric T. Sun ◽  
Julie A. Cler ◽  
Steve J. Mick ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist

scholarly journals Characterization of Metabotropic Glutamate Receptor-Mediated Nitric Oxide Production in Vivo

1997 ◽  
Vol 17 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Anish Bhardwaj ◽  
Frances J. Northington ◽  
Lee J. Martin ◽  
Daniel F. Hanley ◽  
Richard J. Traystman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Calcium Release ◽  
Nmda Receptor Antagonist ◽  
No Production ◽  
Calcium Release Channel ◽  
Mk 801 ◽  
Metabotropic Glutamate

We tested the hypothesis that stimulation of metabotropic glutamate receptors (mGluRs) increases nitric oxide (NO) production in the hippocampus in vivo. Microdialysis probes were placed bilaterally into the CA3 region of the hippocampus of adult Sprague–Dawley rats under pentobarbital anesthesia. Probes were perfused for 5 h with artificial cerebrospinal fluid (CSF) containing 3 μM [14C]-L-arginine. Recovery of [14C]-L-citrulline in the effluent was used as a marker of NO production. In nine groups of rats, increases in [14C]-L-citrulline recovery were compared between right- and left-sided probes perfused with various combinations of the selective mGluR agonist, trans-(1 S,3 R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD); the mGluR antagonist, (±)- α-methyl-4-carboxyphenylglycine (MCPG); the NO synthase inhibitor, N-nitro-L-arginine (LNNA); the ryanodine sensitive calcium-release channel inhibitor dantrolene, the non- N-methyl-D-aspartate (NMDA); receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d] cyclohepten-5,10-imine (MK-801); and the Na+ channel blocker, tetrodotoxin. Recovery of [14C]-L-citrulline during perfusion with artificial CSF progressively increased to 90 ± 21 fmol/min (± SD) over 5 h. Perfusion in the contralateral hippocampus with 1 m M ACPD augmented [14C]-L-citrulline recovery to 250 ± 81 fmol/min. Perfusion of 1 m M nitroarginine + ACPD inhibited [14C]-L-citrulline recovery compared to that with ACPD alone. Perfusion with 1 m M MCPG + ACPD attenuated ACPD enhanced [14C]-L-citrulline recovery. Perfusion of 1 m M dantrolene + ACPD inhibited the ACPD-evoked increase in [14C]-L-citrulline recovery. Perfusion of 1 m M MCPG or dantrolene without ACPD did not decrease [14C]-L-citrulline recovery as compared to CSF alone. ACPD-enhanced [14C]-L-citrulline recovery was not attenuated by CNQX, MK-801, or tetrodotoxin (TTX). Using an indirect method of assessing NO production in vivo, these data demonstrate that mGluR stimulation enhances NO production in rat hippocampus. Inhibition with dantrolene suggests that calcium-induced calcium release amplifies the inositol triphosphate-mediated calcium signal associated with mGluR stimulation, thereby resulting in augmented calcium-dependent NO production.

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