NMDA receptors agonists

NMDA receptor agonists are typically short-chain dicarboxylic amino acids such as glutamate, aspartate and NMDA. Acting at a site on the NR2 subunit, glutamate is the most potent endogenous agonist in the... 

NMDA receptor agonists derived from ibotenic acid. Preparation, neuroexcitation, and neurotoxicity. Eur J Pharmacoi. 189(6) 381-91. 

The precise mechanism by which NO causes glutamase neurotoxicity is unknown. Calcium must be required because of the requirement for NMDA- and glutamate-induced NO formation in brain tissue (Garthwaite etal., 1988). Although both NMDA-receptor agonists and sodium nitroprusside induce specific neurotoxicity as well as cyclic GMP formation in brain tissue (Dawson et al., 1991), it is unlikely that cyclic GMP is the ultimate cause of the neurotoxicity. Instead, NO is most likely involved in producing target cell death. One possible mechanistic pathway is that locally synthesized NO and superoxide anion react with each other to yield peroxynitrite anion (Beckman et al., 1990), which can destroy cell membranes either directly via interaction with cellular thiols (Radi et al., 1991) or indirectly via decomposition to hydroxyl and other free radicals (Beckman et al., 1990). 

Willick, Myma L, and tarry Kokkinidis. 1995. "The Effects of Ventral Tegmental Administration of GABAa, GABA and NMDA Receptor Agonists on Medial Forebrain Bundle Self-Stimulation." Behavioural Brain Research 70 31-36. 

Excitotoxic lesions generated in primates using NMDA receptor agonists such as quinolinic acid cause neuronal loss similar to that found in HD, emphasizing, the potential role of excitotoxicity in HD. Intrastriatal injections of the reversible succinate dehydrogenase inhibitor, malonate, into rats caused a decrease in ATP levels and increased lactate and excitotoxic lesions, which could be prevented by NMDA antagonists. 

Glutamate Decreased presynaptic markers Decreased HC AMPA and kainate receptor expression Minor changes in FC NMDA R sub-units Altered glutamate fibres in cingulate cortex NMDA receptor antagonists produce schizophrenia-like psychosis Roles of NMDA receptors in development and neurotoxicity Partial NMDA receptor agonists have some therapeutic benefits... 

A disturbance of the kynurenine metabolism with an imbalance in favour of the production of the NMDA-receptor agonist quinolinic acid, and... 

The increased levels of quinolinic acid—as NMDA receptor agonist—lead to increased levels of glutamate. Quinolinic acid was shown to cause an overrelease of glutamate in the striatum and in the cortex, presumably by presynaptic mechanisms (Fedele and Foster 1993 Chen et al., 1999). The quinolinic pathway might be the mechanism involved in the increased glutamatergic neurotransmission in MD (Sanacora et al., 2004a). 

Fig. 2. Distribution of twelve large target-specific groups of pharmaceutical agents within the Kohonen map (a) G-protein-coupled receptors (GPCR) agonists/antagonists (5,432 compounds) (b) matrix metalloproteinase inhibitors (120 compounds) (c) tyrosine kinase inhibitors (175 compounds) (d) caspase inhibitors (50 compounds) (e) NMDA receptor agonists/antagonists (150 compounds) (f) potassium channel blockers/activators (302 compounds) ...

Recently, the kynurenine pathway (KP) has been implicated in the pathogenesis of ALS (Chen et al., 2009). The KP is a major route that metabolizes tryptophan and generates its neuroactive intermediates. The metabolic products of tryptophan include quinolinic acid (QUIN), a NMDA receptor agonist and kynurenic acid (KYNA), a neuroprotective NMDA receptor antagonist. In addition to the... 

Fetal guinea pig and newborn piglet model stndies have demonstrated that brain tissue hypoxia results in brain cell membrane damage as evidenced by increased membrane lipid peroxidation and decreased Na+, K+-ATPase activity. Brain hypoxia was found to increase the NMDA receptor agonist-dependent Ca + in synaptosomes of hypoxic as compared to normoxic fetuses (Mishra and Delivoria-Papadopoulos, 1999). 

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