N-methyl-D-aspartic acid receptors

The main building block of PEDC (1 -phenyl-2-[(S)-l-aminoethyl] -N,N -di-ethylcyclopropanecarboxamide), a potent NDMA (N -methyl-D-aspartic acid) receptor antagonist of a cyclopropane structure, N -benzyl-C-cyclopropyl nitrone... 

Ahmed, M . S., Mather, A., Enna, S. J. Binding of pHJdesglycinyl remacemide to rat brain membranes association with the benzomorphan attachment site of the N-methyl-D-aspartic acid receptor channel, Brain Res. 1999, 8, 46-50. 

Eide, P. K., Jorum, E., Stubhaug, A., Bremmes, J., Breivik, H. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine a double-blind, cross-over comparison with morphine and placebo, Pain 1994, 58, 347-354. 

Kleckner, N. W. and Dingledine, R. Requirement for glycine in activation of N-methyl-D-aspartic acid receptors expressed in Xenopus oocytes, Science 1988, 241, 835-837. 

Salituro, F. G., Harrison, B. L., Baron, B. M., Nyce, P. L., Stewart, K. T., Kehne, J. H., White, H. S., McDonald, I. A. 3-(2-Carboxyindol-3-yl)propionic acid-based antagonists of the N-methyl-D-aspartic acid receptor associated glycine binding site, J. Med. Chem. 1992, 35, 1791-1799. 

Dracheva S, Marras SA, Elhakem SL, Kramer FR, Davis KL, et al. 2001. N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia. Am J Psychiatry 158 1400-1410. 

Figure 10.9. Biophysical properties of the N-methyl-D-aspartic acid receptor. The current voltage (i/v) relationship measured in physiological solutions shows a region of negative slope conductance at hyperpolarized potentials. Little inward current is observed until the cell is substantially depolarized. However, when Mg + is removed from the bathing medium the i/v relationship follows Ohm s law and is represented by a straight line. The reason for this behavior is that Mg + block NMDA receptors in a voltage dependent manner (see main text).

Kessler M, Terramani T, Lynch G, Baudry M (1989) A glycine site associated with N-methyl-D-aspartic acid receptors Characterization and identification of a new class of antagonists. J Neurochem 52 1319-1328. 

Wiech K, Kiefer RT, Topfner S, et al. A placebo-controUed randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Anesth Analg 2004 98(2) 408-413. 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

Ibogaine protects the N-methyl-D-aspartate neuron receptors against excessive release of excitatory amino acids and represents, therefore, a potential therapeutic agent for the treatment of Alzheimer s disease, Huntington s chorea, and other... 

Recent progress in chiral analytical chemistry has enabled the analyses of D-amino acids in mammalian tissue. Considerable interest has been generated in D-serine (D-Ser) and D-aspartate (D-Asp), specifically. D-Ser is suggested to have a role in N-methyl- D-aspartate (NMDA) receptor-mediated transmission, and D-Asp is suggested to function as a regulator of hormonal secretion (Hamase et al., 2002). 

Pharmacology Persistent activation of CNS N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer disease. Memantine is an NMDA receptor antagonist. 

Current theories suggest that hypersecretion of cortisol during stress may damage the hippocampus. Studies have demonstrated reduced hippocampal volume in trauma survivors with PTSD, compared to nontrauma tized individuals (Sapolsky, 2000 Bremner, 2001). However, hormonally regulated plasticity in the hippocampus involves multiple influences, and glucocorticoid hormones work in concert with excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors, as well as other neurotransmitters and the GABA-benzodiazepine system (see McEwen, 2000a,b, for review). 

Amantadine appears to work by blocking the N-methyl-D-aspartate (NMDA) receptor in the brain, thereby inhibiting the effects of excitatory amino acids such as glutamate.18,47 This suggests that excitatory neurotransmitters play a role in motor complications associated with advanced Parkinson disease.23,65 Future research may discover other ways of controlling these excitatory neurotransmitters, thus providing additional treatments for people with advanced Parkinson disease. 

As mentioned above, members of the superfamily of ionotropic glutamate receptors are tetramers composed out of a repertoire of at least 18 subunits. They can be categorized into three families N-methyl-D-aspartate (NMDA) receptors, a-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPA) receptors, and kainate receptors, the two latter forming the group of non-NMDA receptors. While NMDA receptors are composed of NR1, -2 (A, B, C, and D), and -3 (A and B)... 

Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298 757-9 Fink K, Gothert M, Molderings G, Schlicker E (1989) N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of noradrenaline release, but not release of other neurotransmitters, in the rat brain cortex receptor location, characterization and desensitization. Naunyn Schmiede-berg s Arch Pharmacol 339 514-21... 

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