Non-NMDA

Antagonists selective for kainate receptors are not available yet. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks AMPA as well as kainate receptors. Nevertheless, compounds like GYKI53655, which acts as a noncompetitive antagonist of AMPA receptors and completely blocks AMPA receptor function at certain concentrations at which no antagonistic effect on kainate receptors is discernible, has been used to demonstrate the kainate receptor-mediated currents in neurons. 

AMPAR. (a-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system. 

Non-NMDA ionotropic glutamate receptors (the majority sodium channel containing) can be subdivided into a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) (comprising cloned subunits GluRl ) and kainate (GluR5-7, KAl-2) preferring receptors, with native receptors most likely to comprise either homo- or heteromeric pentamers of these subunits. 

While there are some reports of increased NMDA and non-NMDA receptor number in various cortical regions of schizophrenics including the prefrontal cortex, there are also indications of impaired glutamate innervation, such as reduction in its neuronal uptake sites (Ishimaru, Kurumaji and Torn 1994). Also it has been found that levels of the mRNA for the NRI subunit of the NMDA receptor in the hippocampus and its D-aspartate binding sites in the temporal cortex are both reduced more on the left than right side in schizophrenic brain. This is another indication of greater malfunction on the left side of the brain and the possibility that some schizophrenic symptoms arise from an imbalance between cross-cortical activity. 

The first allosteric modulators discovered to act on AMPA/KA receptors were the plant lectins, including concanavalin A (ConA), that block receptor desensitization, probably through binding to Y-1 inked oligosaccharides (51,52). It was soon discovered that certain benzothiazides, such as diazoxide and cyclothiazide, also act on the same allosteric site controlling non-NMDA receptor desensitization (53-55). Interestingly, ConA and cyclothiazide show high selectivity for KA and AMPA receptors, respec-... 

Zorumski, C. F., Yamada, K. A., Price, M. T and Olney, J. W. (1993) A benzodiazepine recognition site associated with the non-NMDA glutamate receptor. Neuron 10,61-67. 

Vignes, M. (2001) Regulation of spontaneous inhibitory synaptic transmission by endogenous glutamate via non-NMDA receptors in cultured rat hippocampal neurons. Neuropharmacology 40, 737-748. 

A5 and C primarily project to lamina II and V of the dorsal horn, where they synapse onto local interneurons or directly onto upward-projecting neurons (figure 8.1). These primary afferents release a number of neurotransmitters to relay pain, including glutamate, aspartate, substance P, neurokinin A and B, and calcitonin gene-related peptide (table 8.1). NMDA, non-NMDA and neurokinin receptors are involved in re-... 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Reddy AB, Field MD, Maywood ES Hastings MH 2002 Differential resynchronisation of circadian clock gene expression within the suprachiasmatic nuclei of mice subjected to experimental jet-lag . J Neurosci 22 7326—7330 Schurov IL, McNulty S, Best JD, Sloper PJ, Hastings MH 1999 Glutamatergic induction of CREB phosphorylation and Fos expression in primary cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate activity of NMDA and non-NMDA receptors. J Neuroendocrinol 11 43-51... 

Dysiherbaine, 162, is a biologically active compound containing the hexahydro-2/7-furo[3,2- ]pyran core. Compound 162 acts as a selective agonist of non-NMDA-type glutamate receptors in the central nervous system <20030BC772, 2003SL993>. 

Effects of ethanol and crocin on non-NMDA receptor-mediated synaptic potentials in hippocampal slices... 

The synapic potential mediated by non-NMDA receptors was recorded in normal ACSF. When ethanol (10-50 mM) was added to the perfusing medium, no significant change in non-NMDA receptor-mediated synaptic potential was observed. However, the addition of ethanol at a higher concentration (100 mM) induced a small reduction in non-NMDA receptor-mediated synaptic potential (Fig.(5)A). The reduction in non-NMDA response rapidly occurred after the addition of 100 mM ethanol and reached a steady state within 10 min. After washing out the ethanol, the response gradually returned to the normal level. When 10 pM crocin was added 10 min prior to the ethanol, the non-NMDA response was similarly reduced in the presence of 100 mM ethanol (Fig.(5)B). Crocin (10 pM) did not significantly affect the inhibitory effect of 100 mM ethanol on non-NMDA response (Fig.(5)C) [22],... 

A) Representative experiment showing the effect of ethanol on non-NMDA reseptor-mediated response. (B) Representative experiment showing die influence of crocin on ethanol-induced inhibition of non-NMDA response. Crocin (10 iM) was applied 10 min prior to ethanol (white bar). (C) Concentration-effect curves for ethanol inhibition of non-NMDA response in the absence (O) or presence ( ) of 10 pM crocin. 

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