V-Methyl-D-aspartate

Pyridazino[4,5-d]quinolinediones as novel glycine-V-methyl-D-aspartate antagonists for the treatment of stroke 98JHC1171. 

Long-term potentiation (LTP) is a synaptic plasticity phenomenon that corresponds to an increase in the synaptic strength (increase in the post-synaptic response observed for the same stimulation of the presynaptic terminals) observed after a high frequency stimulation (tetanus) of the afferent fibres. This increased response is still observed hours and even days after the tetanus. The phenomenon is often observed at glutamatergic synapses and involves, in most cases, the activation of the V-methyl D-aspartate (NMDA) subtype of ionotropic glutamate receptors. 

Krystal JH, Petrakis IL, Mason G, et al V-methyl-D-aspartate glutamate receptors and alcoholism reward, dependence, treatment, and vulnerability. Pharmacol Ther 99 79-94, 2003b... 

Bergeron, R, Meyer, TM, Coyle, IT and Greene, RW (1998) Modulation of V-methyl-D-aspartate receptor function by glycine transport. Proc. Natl. Acad. Sci. USA 95 15730-15734. 

FIGURE 1.9 NO production from die CA1 region of die hippocampal slice following addition of 5mM L-glutamate (a) and lOpM /V-methyl-D-aspartate (b). (Reprinted with permission from Elsevier Publishing [50].)... 

V-methyl-D-aspartate (NMDA) receptors have multiple regulatory sites 276... 

V-methyl-D-aspartate (NMDA) receptors have multiple regulatory sites. To date, three NMDA receptor subunit families have been identified, one represented by a single gene (NR1, encoding a protein of -900 amino acids), the... 

V-methyl-D-aspartate receptors. Glutamate is the major excitatory neurotransmitter in the central nervous system (Ch. 15). Its receptors can be divided into three types AMPA/kainate, NMDA and metabotropic receptors. NMDA receptors are composed of two different types of subunit - NR1 and NR2. They play an important role in the induction of synaptic plasticity and excitotoxicity. 

APA, American Psychiatric Association Ca+, calcium Cl", chloride DA, dopamine GABA, ) aminobutyric acid 5-HT, serotonin K+, potassium Na+, sodium NMDA, /V-methyl-D-aspartate NE, norepinephrine. 

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. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

Stoof JC, Booji J, Drukarch B. (1992). Amantadine as /V-methyl-D-aspartic acid receptor antagonist new possibilities for therapeutic applications Clin Neurol Neurosurg. 94(suppl) S4-6. 

Lu C., Chan S. L., Haughey N., Lee W. T., and Mattson M. P. (2001). Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on V-methyl-D-aspartate channels. J. Neurochem. 78 577-589. 

Sacaan, A. I., andjohnson, K. M. (1990). Characterization of the stimulatory and inhibitory effects of polyamines on [3H] N-( -[thienyl] cyclohexyl) piperidine binding to the. V-methyl-D-aspartate receptor ionophore complex. Mol. Pharmacol. 37, 572—577. 

Rodriguez JJ, Garcia DR, Pickel VM. Subcellular distribution of 5-hydroxy-tryptamine2A and V-methyl-D-aspartate receptors within single neurons in rat motor and limbic striatum. J Comp Neurol 1999 413 219-231. 

Buchan A. and Pulsinelli W. A. (1990) Hypothermia but not the V-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J. Neurosci. 10, 311-316. 

Patel, M.N., Yim, G.K.W., Isom, G.E. (1992). Blockade of V-methyl-D-aspartate receptors prevents cyanide-induced neuronal injury in primary hippocampal culture. Toxicol. Appl. Pharmacol. 115 124-9. 

Koyuncouglu, H., Kara, I., Gunel, M. et al. (1998). V-methyl-D-aspartate antagonists, glutamate release inhihitors, 4-anuno-pyridine at neuromuscular transmission. Pharmacol. Res. 37 1-7. 

Parsons, C.G., Danysz, W., Quack, G. (1999). Memantine is a clinically well tolerated V-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data. Neuropharmacology 30 135-67. 

Snyder, S.H. Wolosker, H. Blackshaw, S. Serine racemase a glial enzyme synthesizing D-serine to regulate glutamate-V-methyl-D-aspartate neuro-transmission. Proc. Natl. Acad. Sci. USA 1999, 96, 13,409-13,414. 

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