W-Methyl-D-aspartate

Similarly, W-methyl-D-aspartate (NMDA) antagonists 32 with analgesic activity were prepared, again using the Meth-Cohn quinoline synthesis as the key entry reaction, subsequent functional group manipulation giving the desired target compound. 

The acquisition of spatial and temporal memory is associated with excitatory synaptic plasticity involving hippocampal W-methyl-D-aspartate (NMDA) receptors (Morris et al. 1986, 1989 Davis et al. 1992 McHugh et al. 1996 Tsien et al. 1996 Huerta et al. 2000 Nakazawa et al. 2002 Tang et al. 1999). Recently,... 

Taylor [173] showed that EGb acts in vitro as an inhibitor of radioligand binding to the competitive and non-competitive sites of W-methyl-D-aspartate (NMDA) receptors. In addition, the most potent inhibition (Kj = 0.5 mgAnl) is observed for non-competitive NMDAsites labeled by [3H]MK-80l. 

Gallagher M. J., Huang H., Pritchett D. B., and Lynch D. R. (1996). Interactions between ifenprodil and the NR2B subunit of the W-methyl-D-aspartate receptor. J. Biol. Chem. 271 9603-9611. 

Summary of negative symptom change across clinical trials in which W-methyl-D-aspartate (NMDA) full agonists (glycine, D-serine, D-alanine) or the glycine transport inhibitor sarcosine have been used in combination with antipsychotics other than clozapine (Originally published in Javitt (2008))... 

FIGURE 15.39 Bioisosteric replacements of the phenol function in the design of W-methyl-D-aspartate (NMDA) receptor antagonists. 

Watanabe M, Mishina M, Inoue Y (1994c) Distinct spatiotemporal distributions of the W-methyl-D-aspartate receptor channel subunit mRNAs in the mouse cervical cord. J Comp Neurol 345 314-319. 

A. Feibamate has effects on sodium channels, enhances activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and blocks W-methyl-D-aspartate (NMDA) receptors. 

W-Methyl-D-aspartic acid (NMDA) receptor is an NMDA-sensitive ionotropic glutamate receptor that plays an important role in synaptic modulation and memory function. Antagonism of NMDA receptor by eugenol [53] might result in its presumed inhibition of synaptic plasticity [49] or contribute to its anesthetic ability. 

Remember that W-methyl-D-aspartic acid is a neuroexcitator comparable to domoic acid and kainic acid (Sato eta ., 1996). Figure 12.4 Examples of amino acids, amines, and betaines isolated from Chlorophyceae... 

Antonov S. M. and Johnson J. W., Permeant ion regulation of IV-methyl-D-aspartate receptor channel block by Mg(2+). Proc. Natl. Acad. Sci., 96, 14571-14576, 1999. 

Peters, S., Koh, J., and Choi, D. W. (1987) Zinc selectively blocks the action of V-methyl-D-aspartate on cortical neurons. Science 236, 589-593. 

Moaddel, R., Clorx, J.-F., Ertem, G., Wainer, I. W. Multiple receptor liquid chromatographic stationary phases the co-immobilization of nicotinic receptors, y-amino-butyric acid receptors, and N-methyl-D-aspartate receptors. Pharm Res 2002, 19, 104-107. 

Bach, A., Chi, C.N., Olsen, T.B., Pedersen, S.W., Roder, M.U., Pang, G.F., Clausen, R.P., Jemth, P. and Stromgaard, K. (2008) Modified Peptides as Potent Inhibitors offhe Postsynaptic Density-95/ N-Methyl-d-Aspartate Receptor Interaction. Journal of Medicinal Chemistry, 51, 6450-6459. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Holter SM, Danysz W, Spanagel R (2000) Novel uncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist MRZ 2/579 suppresses ethanol intake in long-term ethanol-experienced rats and generalizes to ethanol cue in drug discrimination procedure. J Pharmacol Exp Ther 292 545-552... 

Parsons CG, Danysz W, Quack G (1998) Glutamate in CNS disorders as a target for drug development. An update. Drug News Perspect 11 523-569 Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38 735-767... 

Chizh, B. A., Schlutz, H., Scheed, M., Englberger, W. The N-methyl-D-aspartate antagonistic and opioid components of D-methadone antinociception in the rat spinal cord, Neurosci. Lett. 2000, 296, 117-120. 

Danysz, W., Fadda, E., Wroblewski, J. T., Costa, E. Kynurenate and 2-amino-5-phosphonovalerate interact with multiple binding sites of the N-methyl-D-aspartate-sensitive glutamate receptor complex, Neurosci. Lett. 1989, 96, 340-344. 

Danysz, W. and Parsons, C. G. Glycine and N-methyl-D-aspartate receptors Physiological significance and possible therapeutic applications, Pharmacol. Rev. 1998, 50, 597-664. 

Henderson, G., Johnson, J. W., Ascher, P. Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor, J. Physiol. 1990, 430, 189-212. 

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. 

Leem, J. W., Choi, E. J., Park, E. S., Paik, K. S. N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists differentially suppress dorsal horn neuron responses to mechanical stimuli in rats with peripheral nerve injury, Neurosci. Lett. 1996, 211, 37-40. 

Leeson, P. D., Carling, R. W., James, K., Smith, J. D., Moore, K. W., Wong, E. H. F., Baker, R. Role of hydrogen binding in ligand interaction with the N-methyl-D-aspartate receptor ion channel, J. 

Leonard, A. S. and Hell, J. W. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites, J. Biol. Chem. 1997, 272, 12107-12115. 

Ortwine D. F., Malone, T. C., Bigge, C. F., Drummond, J. T., Humblet, C., Johnson, G., Pinter, G. W. Generation of N-methyl-D-aspartate agonist and competitive antagonist pharmacophor models. 

Parsons, C. G, Danysz, W., Quack, G. Memantine is a clinically well tolerated N-methyl-D-aspartate... 

Perkins, M., Rudin, M., Sauter, A., Wiederhold, K.-H., Muller, W. Biphenyl-derivatives of2-amino-7-phosphono-heptanoic acid A novel class of potent competitive N-methyl-D-aspartate receptor antagonists II. Pharmacological characterization in vivo, Neuropharmacology 1996, 35, 655-669. 

Woodward, R. M., Huettner, J. E., Guastella, J., Keana, J. F. W., Weber, E. In vitro pharmacology of ACEA-1021 and ACEA-1031 systemically active quinoxalinedioneswith high affinity and selectivity for N-methyl-D-aspartate receptor glycine sites, Mol. Pharmacol. 1995b, 47, 568-581. 

Olney J. W. (1989). Excitotoxicity and N-methyl-D-aspartate receptors. Drug Dev. Res. 17 299-319. 

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