Pharmacological Reviews xPharm- The Comprehensive Pharmacology Reference
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Danysz, W.
Right arrow Articles by Parsons, C. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Danysz, W.
Right arrow Articles by Parsons, C. G.

Vol. 50, Issue 4, 597-664, December 1998

Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications

Wojciech Danysza and Chris G. Parsons

Department of Pharmacological Research, Merz and Co., Frankfurt/M, Germany

I. Introduction
II. N-Methyl-D-Aspartate Receptors
    A. Basic Characteristics
    B. NR1 Splice Variants
    C. Distribution and Ontogeny
    D. Glutamate and Glycine Binding Sites
III. Physiological Role of Glycine
    A. Glycine as a Coagonist
    B. Desensitization
    C. Endogenous Agonists: Glycine and/or D-Serine
        1. Distribution within the central nervous system.
        2. Uptake.
        3. Release.
        4. Source and synthesis.
        5. Metabolism.
        6. N-Methyl-D-aspartate receptor-coupled recognition site and its distribution.
        7. Are glycineB sites saturated in vivo?
    D. Kynurenic Acid as an Endogenous Antagonist of the GlycineB Site
IV. Exogenous Ligands
    A. Agonists of the GlycineB Site
    B. Partial Agonists of the GlycineB Site
    C. Antagonists
        1. Kynurenic acid derivatives.
        2. 2-Carboxyindoles.
        3. 2-Carboxytetrahydroquinolines.
        4. 4-Hydroxy-2-quinolones.
        5. Quinoxaline-2,3-diones.
        6. 3-Hydroxy-1H-1-benzazepine-2,5-diones.
        7. Tricyclic glycineB site antagonists.
        8. Prodrugs.
        9. Modification of endogenous kynurenic acid metabolism.
    D. Implications
    E. 3H-Radiolabeled Ligands for the GlycineB Site
    F. Allosteric Interactions Involving the GlycineB Site
V. N-Methyl-D-Aspartate Receptor Subtypes: Differences in GlycineB Recognition Sites
VI. Therapeutic Aspects for Agents Acting at the GlycineB Site
    A. Pharmacokinetic Aspects
    B. Side Effects
        1. Drug discrimination.
        2. Learning impairment.
        3. Ataxia, myorelaxation, and sedation.
        4. Neurotoxicity in the retrosplenial/cingulate cortex.
        5. Psychotomimetic side effects.
    C. Anxiety
    D. Depression
    E. Schizophrenia
    F. Convulsions and Epilepsy
    G. Drug Dependence and Tolerance
        1. Opioids.
        2. Cocaine.
    H. Pain
    I. Ethanol Dependence and Abuse
    J. Huntington's Disease
    K. Alzheimer's Disease and Dementia
    L. Parkinson's Disease
    M. Neuroprotection Against Acute Insults
        1. Introduction.
        2. Ischemia.
    N. Other Neurodegenerative Diseases
VII. First Clinical Experiences with GlycineB Antagonists
VIII. Concluding Remarks
Acknowledgments
References

a   Address for correspondence: Wojciech Danysz, Department of Pharmacological Research, Merz and Co., Eckenheimer Landstrasse 100-104, 60318 Frankfurt/M, Germany. E-mail: wojciech.danysz{at}merz.de.

0031-6997/98/5004-0597$03.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Clin. Chem.Home page
S. A. Fuchs, M. G. M. de Sain-van der Velden, M. M. J. de Barse, M. W. Roeleveld, M. Hendriks, L. Dorland, L. W. J. Klomp, R. Berger, and T. J. de Koning
Two Mass-Spectrometric Techniques for Quantifying Serine Enantiomers and Glycine in Cerebrospinal Fluid: Potential Confounders and Age-Dependent Ranges
Clin. Chem., September 1, 2008; 54(9): 1443 - 1450.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
T. Suwabe, H. Fukami, and R. M. Bradley
Synaptic Responses of Neurons Controlling the Parotid and von Ebner Salivary Glands in Rats to Stimulation of the Solitary Nucleus and Tract
J Neurophysiol, March 1, 2008; 99(3): 1267 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
M. Oda, S. Kure, T. Sugawara, S. Yamaguchi, K. Kojima, T. Shinka, K. Sato, A. Narisawa, Y. Aoki, Y. Matsubara, et al.
Direct Correlation Between Ischemic Injury and Extracellular Glycine Concentration in Mice With Genetically Altered Activities of the Glycine Cleavage Multienzyme System
Stroke, July 1, 2007; 38(7): 2157 - 2164.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
H. Wolosker
D-Serine Regulation of NMDA Receptor Activity
Sci. Signal., October 10, 2006; 2006(356): pe41 - pe41.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
A. B. Alex, A. J. Baucum, and K. S. Wilcox
Effect of Conantokin G on NMDA Receptor-Mediated Spontaneous EPSCs in Cultured Cortical Neurons
J Neurophysiol, September 1, 2006; 96(3): 1084 - 1092.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Dumin, I. Bendikov, V. N. Foltyn, Y. Misumi, Y. Ikehara, E. Kartvelishvily, and H. Wolosker
Modulation of D-Serine Levels via Ubiquitin-dependent Proteasomal Degradation of Serine Racemase
J. Biol. Chem., July 21, 2006; 281(29): 20291 - 20302.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Bull.Home page
T. J. Ha, A. B. Kohn, Y. V. Bobkova, and L. L. Moroz
Molecular Characterization of NMDA-Like Receptors in Aplysia and Lymnaea: Relevance to Memory Mechanisms
Biol. Bull., June 1, 2006; 210(3): 255 - 270.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Kartvelishvily, M. Shleper, L. Balan, E. Dumin, and H. Wolosker
Neuron-derived D-Serine Release Provides a Novel Means to Activate N-Methyl-D-aspartate Receptors
J. Biol. Chem., May 19, 2006; 281(20): 14151 - 14162.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. K. Yee, E. Balic, P. Singer, C. Schwerdel, T. Grampp, L. Gabernet, I. Knuesel, D. Benke, J. Feldon, H. Mohler, et al.
Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile.
J. Neurosci., March 22, 2006; 26(12): 3169 - 3181.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
H. K. Park, Y. Shishido, S. Ichise-Shishido, T. Kawazoe, K. Ono, S. Iwana, Y. Tomita, K. Yorita, T. Sakai, and K. Fukui
Potential Role for Astroglial D-Amino Acid Oxidase in Extracellular D-Serine Metabolism and Cytotoxicity
J. Biochem., February 1, 2006; 139(2): 295 - 304.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Shleper, E. Kartvelishvily, and H. Wolosker
D-Serine Is the Dominant Endogenous Coagonist for NMDA Receptor Neurotoxicity in Organotypic Hippocampal Slices
J. Neurosci., October 12, 2005; 25(41): 9413 - 9417.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
C. R. Yang and L. Chen
Targeting Prefrontal Cortical Dopamine D1 and N-Methyl-D-Aspartate Receptor Interactions in Schizophrenia Treatment
Neuroscientist, October 1, 2005; 11(5): 452 - 470.
[Abstract] [PDF]

Home page
 IOVSHome page
M. Lamas, I. Lee-Rivera, and A. M. Lopez-Colome
Cell-specific Expression of N-Methyl-D-Aspartate Receptor Subunits in Muller Glia and Neurons from the Chick Retina
Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3570 - 3577.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. Martina, M.-E. B.-Turcotte, S. Halman, G. Tsai, M. Tiberi, J. T Coyle, and R. Bergeron
Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice
J. Physiol., March 15, 2005; 563(3): 777 - 793.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. N. Foltyn, I. Bendikov, J. De Miranda, R. Panizzutti, E. Dumin, M. Shleper, P. Li, M. D. Toney, E. Kartvelishvily, and H. Wolosker
Serine Racemase Modulates Intracellular D-Serine Levels through an {alpha},{beta}-Elimination Activity
J. Biol. Chem., January 21, 2005; 280(3): 1754 - 1763.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
D. J. Posey, D. L. Kem, N. B. Swiezy, T. L. Sweeten, R. E. Wiegand, and C. J. McDougle
A Pilot Study of D-Cycloserine in Subjects With Autistic Disorder
Am J Psychiatry, November 1, 2004; 161(11): 2115 - 2117.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
H. Huang, L. Barakat, D. Wang, and A. Bordey
Bergmann glial GlyT1 mediates glycine uptake and release in mouse cerebellar slices
J. Physiol., November 1, 2004; 560(3): 721 - 736.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
R. Lim, P. Hoang, and A. J. Berger
Blockade of Glycine Transporter-1 (GLYT-1) Potentiates NMDA Receptor-Mediated Synaptic Transmission in Hypoglossal Motorneurons
J Neurophysiol, October 1, 2004; 92(4): 2530 - 2537.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. W. Polli, T. M. Baughman, J. E. Humphreys, K. H. Jordan, A. L. Mote, L. O. Webster, R. J. Barnaby, G. Vitulli, L. Bertolotti, K. D. Read, et al.
THE SYSTEMIC EXPOSURE OF AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST IS LIMITED IN MICE BY THE P-GLYCOPROTEIN AND BREAST CANCER RESISTANCE PROTEIN EFFLUX TRANSPORTERS
Drug Metab. Dispos., July 1, 2004; 32(7): 722 - 726.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Tsai, R. J. Ralph-Williams, M. Martina, R. Bergeron, J. Berger-Sweeney, K. S. Dunham, Z. Jiang, S. B. Caine, and J. T. Coyle
Gene knockout of glycine transporter 1: Characterization of the behavioral phenotype
PNAS, June 1, 2004; 101(22): 8485 - 8490.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. Martina, Y. Gorfinkel, S. Halman, J. A. Lowe, P. Periyalwar, C. J. Schmidt, and R. Bergeron
Glycine transporter type 1 blockade changes NMDA receptor-mediated responses and LTP in hippocampal CA1 pyramidal cells by altering extracellular glycine levels
J. Physiol., June 1, 2004; 557(2): 489 - 500.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Ju, K. R. Aubrey, and R. J. Vandenberg
Zn2+ Inhibits Glycine Transport by Glycine Transporter Subtype 1b
J. Biol. Chem., May 28, 2004; 279(22): 22983 - 22991.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Alkondon, E. F. R. Pereira, P. Yu, E. Z. Arruda, L. E. F. Almeida, P. Guidetti, W. P. Fawcett, M. T. Sapko, W. R. Randall, R. Schwarcz, et al.
Targeted Deletion of the Kynurenine Aminotransferase II Gene Reveals a Critical Role of Endogenous Kynurenic Acid in the Regulation of Synaptic Transmission via {alpha}7 Nicotinic Receptors in the Hippocampus
J. Neurosci., May 12, 2004; 24(19): 4635 - 4648.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
T. A. Simeone, R. M. Sanchez, and J. M. Rho
Molecular Biology and Ontogeny of Glutamate Receptors in the Mammalian Central Nervous System
J Child Neurol, May 1, 2004; 19(5): 343 - 360.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
G. G. Kinney, C. Sur, M. Burno, P. J. Mallorga, J. B. Williams, D. J. Figueroa, M. Wittmann, W. Lemaire, and P. J. Conn
The Glycine Transporter Type 1 Inhibitor N-[3-(4'-Fluorophenyl)-3-(4'-Phenylphenoxy)Propyl]Sarcosine Potentiates NMDA Receptor-Mediated Responses In Vivo and Produces an Antipsychotic Profile in Rodent Behavior
J. Neurosci., August 20, 2003; 23(20): 7586 - 7591.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Foucaud, B. Laube, R. Schemm, A. Kreimeyer, M. Goeldner, and H. Betz
Structural Model of the N-Methyl-D-aspartate Receptor Glycine Site Probed by Site-directed Chemical Coupling
J. Biol. Chem., June 20, 2003; 278(26): 24011 - 24017.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
M. S. Wallace, M. C. Rowbotham, N. P. Katz, R. H. Dworkin, R. M. Dotson, B. S. Galer, R. L. Rauck, M. M. Backonja, S. N. Quessy, and P. D. Meisner
A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain
Neurology, December 10, 2002; 59(11): 1694 - 1700.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. P. Cook, I. Galve-Roperh, A. Martinez del Pozo, and I. Rodriguez-Crespo
Direct Calcium Binding Results in Activation of Brain Serine Racemase
J. Biol. Chem., July 26, 2002; 277(31): 27782 - 27792.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
K. A. Haberny, M. G. Paule, A. C. Scallet, F. D. Sistare, D. S. Lester, J. P. Hanig, and W. Slikker Jr.
Ontogeny of the N-Methyl-D-Aspartate (NMDA) Receptor System and Susceptibility to Neurotoxicity
Toxicol. Sci., July 1, 2002; 68(1): 9 - 17.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
J.-M. Orgogozo, A.-S. Rigaud, A. Stoffler, H.-J. Mobius, and F. Forette
Efficacy and Safety of Memantine in Patients With Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300)
Stroke, July 1, 2002; 33(7): 1834 - 1839.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Panizzutti, J. De Miranda, C. S. Ribeiro, S. Engelender, and H. Wolosker
A new strategy to decrease N-methyl-D-aspartate (NMDA) receptor coactivation: Inhibition of D-serine synthesis by converting serine racemase into an eliminase
PNAS, April 12, 2001; (2001) 91002298.
[Abstract] [Full Text]

Home page
 Arch Gen PsychiatryHome page
D. C. Javitt, U. Heresco-Levy, N. B. Farber, J. W. Newcomer, and J. W. Olney
Are Glycine Sites Saturated In Vivo?
Arch Gen Psychiatry, December 1, 2000; 57(12): 1181 - 1183.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-P. Mothet, A. T. Parent, H. Wolosker, R. O. Brady Jr., D. J. Linden, C. D. Ferris, M. A. Rogawski, and S. H. Snyder
D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor
PNAS, April 25, 2000; 97(9): 4926 - 4931.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Wolosker, S. Blackshaw, and S. H. Snyder
Serine racemase: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission
PNAS, November 9, 1999; 96(23): 13409 - 13414.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. B. Hesselink, H. Smolders, B. Eilbacher, A. G. De Boer, D. D. Breimer, and W. Danysz
The Role of Probenecid-Sensitive Organic Acid Transport in the Pharmacokinetics of N-Methyl-D-Aspartate Receptor Antagonists Acting at the GlycineB-Site: Microdialysis and Maximum Electroshock Seizures Studies
J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 543 - 550.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
M. Kumari
Differential Effects of Chronic Ethanol Treatment on N-Methyl-D-aspartate R1 Splice Variants in Fetal Cortical Neurons
J. Biol. Chem., August 3, 2001; 276(32): 29764 - 29771.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Panizzutti, J. De Miranda, C. S. Ribeiro, S. Engelender, and H. Wolosker
A new strategy to decrease N-methyl-D-aspartate (NMDA) receptor coactivation: Inhibition of D-serine synthesis by converting serine racemase into an eliminase
PNAS, April 24, 2001; 98(9): 5294 - 5299.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition