Search results for "NMDA"

A Novel Series of 2-Carboxytetrahydroquinolines Provides New Insights into the Eastern Region of Glycine Site NMDA Antagonists

2000

A series of potent 4-substituted tetrahydroquinolines has been synthesized and biologically tested in order to refine the eastern region of the pharmacophore model for glycine site NMDA antagonists concerning the assessment of lipophilicity, flexibility, and hydrogen bonding. Displacement studies on rat cortical membranes using [ 3 H]-5,7-dichlorokynurenic acid as a radioligand indicated that binding affinities are markedly enhanced when additional hydrogen-accepting groups are introduced into the eastern region of the 2-carboxytetrahydroquinolines. Among the most potent ligands were some urea, sulfonylurea, and crown ether compounds as interesting leads for new diagnostics, especially for …

NMDA receptor antagonist treatment induces a long-lasting increase in the number of proliferating cells, PSA-NCAM-immunoreactive granule neurons and …

2001

During adulthood, neural precursors located in the subgranular zone of the dentate gyrus continue to proliferate, leading to the generation of new granule neurons. These recently generated cells transiently express the polysialylated form of the neural cell adhesion molecule, PSA-NCAM, and are supported by radial glia-like cells that are likely to play a role in neuronal migration and differentiation, or even act as their precursors. Previous reports indicate that treatment with NMDA receptor antagonists stimulates adult neurogenesis in the dentate gyrus, and because of the potential therapeutic value of this approach, we were interested in further characterizing the consequences of pharmac…

Data from: NMDA receptor antagonists and pain relief: a meta-analysis of experimental trials

2019

OBJECTIVES: We conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of N-methyl-D-aspartate receptor (NMDAR) antagonists. METHODS: Six major databases were systematically searched (to 03/2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis. RESULTS: Searches identified 70 eligible trials (N=1069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in the size of hyperalgesic area (Standardized Mean Difference=0.54, CI95[0.34, 0.74], p<.001), and a 1.2-poin…

Altered receptor binding densities in experimental antiphospholipid syndrome despite only moderately enhanced autoantibody levels and absence of beha…

2013

Abstract Experimental antiphospholipid syndrome (eAPS) in Balb/c mice causes neuropsychiatric abnormalities including hyperactivity, increased explorative behavior and cognitive deficits. Recently, we have demonstrated that these behavioral changes were linked to an upregulation of serotonergic 5-HT1A receptor binding densities in cortical and hippocampal regions while excitatory and inhibitory neurotransmitter receptors remain largely unchanged. To examine whether the observed behavioral features depend on a critical antibody concentration, mice with only moderately enhanced antiphospholipid antibodies (aPL), about 50–80% of high levels, were analyzed and compared to controls. The staircas…

P1296 : Blocking NMDA receptors prolongs survival in rats with acute liver failure by dual protective mechanisms in kidney and brain

2015

were 1094.67±239.37mIU/ml. The difference in values between these groups was statistically significant (p = 0.004). There was a statistically significant difference in total leucocyte count, serum creatinine, INR and cleaved CK18 M30 levels among those that survived vs expired. Multivariate analysis found that all these independently predict mortality. A receiver operating characteristic curve was drawn for the new score. The score found was compared with the King’s College criteria and the MELD score, the new scoring system was found to have higher sensitivity and specificity for mortality compared with other standard prognostic markers in ALF, and has a better diagnostic accuracy (Table 1…

89. Loss of extinction in CA1-NMDA receptor deficient mice: A novel model for PTSD?

2009

NMDA-induced acetylcholine release in mouse striatum: role of NO synthase isoforms

2002

Striatal cholinergic interneurons are stimulated by glutamatergic inputs from thalamus and cortex via NMDA receptors. The present microdialysis study was designed to characterize the role of nitric oxide (NO) in this process and to identify the NO synthase (NOS) isoform responsible for this effect. For this purpose, we studied the effects of NMDA and 3-morpholino sydnonimine (SIN-1) perfusions on the release of acetylcholine (ACh) in mouse striatum. In wild-type C57/Bl6 mice, perfusion of NMDA (100 µm) induced a two-fold stimulation of ACh release. This effect was attenuated in mice lacking endothelial NOS but was completely absent in mice lacking neuronal NOS. Local perfusion of SIN-1 (300…

The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency

2018

AbstractAlzheimer’s disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ 40 secretion. Single intrape…

Induction of neurosteroid synthesis by NMDA receptors in isolated rat retina: a potential early event in excitotoxicity

1998

Here we investigated the possible regulation of neurosteroidogenesis by N-methyl-D-aspartic acid (NMDA) receptor activation and addressed the hypothesis that neurosteroid synthesis may be involved in acute excitotoxicity. In the isolated retina, exposure to NMDA modified pregnenolone and pregnenolone sulphate formation. This effect was dose and time dependent, the synthesis being increased by relatively moderate NMDA doses (1-100 microM) within 30 min exposure and reduced to its control value by 60 min or by raising drug concentrations. NMDA-stimulated neurosteroid synthesis was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) and 3(2-ca…

Pregnenolone sulfate modulates NMDA receptors, inducing and potentiating acute excitotoxicity in isolated retina

1998

Pregnenolone sulfate (PS) acts as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptor-mediated responses. In the retina, we previously observed that the synthesis of pregnenolone and PS increases after stimulation of NMDA receptors and blockade of the synthesis reduces retinal cell death. This study was carried out to explore in the isolated and intact retina the possible role of PS in NMDA-induced excitotoxicity. Lactate dehydrogenase (LDH) measurements and morphological analysis revealed that a 90-min exogenous application of PS at 0.1-500 microM concentrations potentiated NMDA-induced cell death and at 50-500 microM concentrations caused cytotoxicity. After 45 min, ei…