Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-29T03:08:33.792Z Has data issue: false hasContentIssue false

4 - Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Chrysanthy Ikonomidou  and
Lechoslaw Turski
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Chrysanthy Ikonomidou
Affiliation:
Department of Pediatric Neurology, Carl Gustav Carus University, Dresden, Germany
Lechoslaw Turski
Affiliation:
Solvay Pharmaceuticals Research Laboratories, Weesp, the Netherlands
Get access

Summary

Introduction

In 1935 Krebs discovered that the amino acid glutamate increases metabolism in the isolated retina and that it is concentrated in the cerebral gray matter (Krebs, 1935). Hayashi (1952, 1958) first reported on excitatory properties of glutamate on neuronal tissue. Local administration of glutamate on the motor cortex of dogs and primates resulted in motor seizures. Curtis et al. (1959) subsequently demonstrated that glutamate and aspartate, when applied iontophoretically to the cat spinal cord, depolarized neurons. Since the 1960s there has been appreciation of the role of glutamate in the nervous system, and today it is considered the major excitatory neurotransmitter (Fonnum, 1984). It is essential for learning and memory, synaptic plasticity, neuronal survival and, in early development, for proliferation, migration and differentiation of neuronal progenitors and immature neurons (Guerrini et al., 1995; Ikonomidou et al., 1999; Komuro & Rakic, 1993).

Glutamate fulfils its various functions due to its compartmentalization (Fonnum, 1984). The largest pool of glutamate is the metabolic pool. The neuronal pool is located in nerve endings and represents the neurotransmission pool. A separate pool is located in glia and serves the recycling of transmitter glutamate. The smallest glutamate pool is involved in synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Glutamate is released from presynaptic terminals by a calcium-dependent mechanism, is removed subsequently by uptake into the surrounding glial cells and aminated to glutamine.

When released into the synaptic cleft, glutamate acts at the postsynaptic site on receptors (Hollmann & Heinemann, 1994; Nakanishi, 1992).

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 44 - 56
Publisher: Cambridge University Press
Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adler, C. H., Stern, M. B., Vernon, G. & Hurtig, H. I. (1997). Amantadine in advanced Parkinson's disease: good use of an old drug. J. Neurol., 244, 336–7CrossRefGoogle ScholarPubMed
Akbar, M. T., Torp, R., Danbolt, N. C., Levy, L. M., Meldrum, B. S. & Ottersen, O. P. (1997). Expression of glial glutamate transporters GLT-1 and GLAST is unchanged in the hippocampus in fully kindled rats.Neuroscience, 78, 351–9CrossRefGoogle ScholarPubMed
Andersen, P. M. (2001). Genetics of sporadic ALS. Amyotroph. Lateral Scler. Other Motor Neuron Disord., 2, S37–41Google ScholarPubMed
Andersen, P. M., Morita, M. & Brown, R. H. Jr. (2001). Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Genomics, 78, 178–84CrossRefGoogle Scholar
Arias, C., Arrieta, I. & Tapia, R. (1995). beta-Amyloid peptide fragment 25–35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices. J. Neurosci. Res., 41, 561–6CrossRefGoogle ScholarPubMed
Bartus, R. T., Baker, K. L., Heiser, A. D.et al. (1994). Postischemic administration of AK275, a calpain inhibitor, provides substantial protection against focal ischemic brain damage. J. Cereb. Blood Flow Metab., 14, 537–44CrossRefGoogle ScholarPubMed
Beal, M. F. (1992a). Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?Ann. Neurol., 31, 119–30CrossRefGoogle Scholar
Beal, M. F. (1992b). Role of excitotoxicity in human neurological disease. Curr. Opin. Neurol., 2, 657–62CrossRefGoogle Scholar
Beal, M. F., Kowall, N. W., Ellison, D. W., Mazurek, M. F., Swartz, K. J. & Martin, J. B. (1986). Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature, 321, 168–71CrossRefGoogle ScholarPubMed
Beal, M. F., Ferrante, R. J., Swartz, K. J. & Kowall, N. W. (1991a). Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. J. Neurosci., 11, 1649–59CrossRefGoogle Scholar
Beal, F., Swartz, K. J., Hyman, B. T., Storey, E., Finn, S. F. & Koroshetz, W. (1991b). Aminooxyacetic acid results in excitotoxic lesions by a novel indirect mechanism. J. Neurochem., 57, 1068–73CrossRefGoogle Scholar
Beal, M. F., Brouillet, E., Jenkins, B., Henshaw, R., Rosen, B. & Hyman, B. T. (1993a). Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate. J. Neurochem., 61, 1147–50CrossRefGoogle Scholar
Beal, M. F., Brouillet, E., Jenkins, B. G.et al. (1993b). Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3- nitropropionic acid. J. Neurosci., 13, 4181–92CrossRefGoogle Scholar
Beckman, J. S., Ischiropoulos, H., Zhu, L.et al. (1992). Kinetics of superoxide-dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch. Biochem. Biophys., 298, 438–45CrossRefGoogle ScholarPubMed
Bensimon, G., Lacomblez, L., Meininger, V. & The ALS/Riluzole Study Group. (1994). A controlled trial of riluzole in amyotrophic lateral sclerosis. N. Engl. J. Med., 330, 585–91CrossRefGoogle ScholarPubMed
Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. & Seitelberger, F. (1973). Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. Neurol. Sci., 20, 415–55CrossRefGoogle ScholarPubMed
Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V. & Greenamyre, J. T. (2000). Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci., 3, 1301–6CrossRefGoogle ScholarPubMed
Blum, D., Torch, S., Lambeng, N.et al. (2001). Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog. Neurobiol., 65, 135–72CrossRefGoogle ScholarPubMed
Borasio, G. D., Robberecht, W., Leigh, P. N.et al. (1998). A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF- I Study Group. Neurology, 51, 583–6CrossRefGoogle ScholarPubMed
Borlongan, C. V., Koutouzis, T. K. & Sanberg, P. R. (1997). 3-Nitropropionic acid animal model and Huntington's disease. Neurosci. Biobehav. Rev., 21, 289–93CrossRefGoogle ScholarPubMed
Bowen, B. C., Block, R. E., Sanchez-Ramos, J.et al. (1994). Proton MR spectroscopy of the brain in 14 patients with Parkinson's disease. Am. J. Neuroradiol., 16, 61–8Google Scholar
Braak, H., Braak, E. & Bohl, J. (1993). Staging of Alzheimer-related cortical destruction. Eur. Neurol., 33, 403–8CrossRefGoogle ScholarPubMed
Brooks, D. J. (1998). The early diagnosis of Parkinson's disease. Ann. Neurol., 44 (Suppl), S10–18CrossRefGoogle ScholarPubMed
Brorson, J. R., Bindokas, V. P., Iwama, T., Marcuccilli, C. J., Chisholm, J. C. & Miller, R. J. (1995). The Ca2+ influx induced by beta-amyloid peptide 25–35 in cultured hippocampal neurons results from network excitation. J. Neurobiol., 26, 325–38CrossRefGoogle ScholarPubMed
Brouillet, E. & Beal, M. F. (1993). NMDA antagonists partially protect against MPTP induced neurotoxicity in mice. NeuroReport, 4, 387–90CrossRefGoogle ScholarPubMed
Brouillet, E., Hantraye, P., Ferrante, R. J.et al. (1995). Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc. Natl. Acad. Sci., USA, 92, 7105–9CrossRefGoogle ScholarPubMed
Brune, B. & Lapetina, E. G. (1989). Activation of a cytosolic ADP-ribosyl transferase by nitric oxide generating agents. J. Biol. Chem., 264, 8455–8Google Scholar
Burnashev, N., Schoepfer, R., Monyer, H.et al. (1992). Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptors. Science, 257, 1415–19CrossRefGoogle Scholar
Calne, D. B. & Langston, J. W. (1983). Aetiology of Parkinson's disease. Lancet, ii, 1457–9CrossRefGoogle Scholar
Chan, P., Langston, J. W. & Monte, D. A. (1993). MK-801 temporarily prevents MPTP-induced acute dopamine depletion and MPP+ elimination in the mouse striatum. J. Pharmacol. Exp. Ther., 267, 1515–20Google ScholarPubMed
Chatterton, J. E., Awobuluyi, M., Premkumar, L. S.et al. (2002). Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature, 415, 793–8CrossRefGoogle ScholarPubMed
Chen, Y. I., Jenkins, B. G. & Rosen, B. R. (1994). Evidence for impairment of energy metabolism in Parkinson's disease using in vivo localized MR spectroscopy. Proc. Soc. Magn. Res., 1, 194Google Scholar
Choi, D. W. (1987). Ionic dependence of glutamate neurotoxicity. J. Neurosci., 7, 369–79CrossRefGoogle ScholarPubMed
Choi, D. W., Maulucci-Gedde, M. & Kriegstein, A. R. (1987). Glutamate neurotoxicity in cortical cell culture. J. Neurosci., 7, 357–68CrossRefGoogle ScholarPubMed
Clancy, R. M., Levartovsky, D., Leszczynska-Piziak, J., Yegudin, J. & Abramson, S. B. (1994). Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: Evidence for S-nitrosoglutathione as a biactive intermediary. Proc. Natl Acad. Sci., USA, 91, 3680–4CrossRefGoogle Scholar
Cleveland, D. W. & Rothstein, J. D. (2001). From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci., 2, 806–19CrossRefGoogle ScholarPubMed
Corson, L. B., Strain, J. J., Culotta, V. C. & Cleveland, D. W. (1998). Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants. Proc. Natl Acad. Sci., USA, 95, 6361–6CrossRefGoogle ScholarPubMed
Couratier, P., Hugon, J., Sindou, P., Vallat, J. M. & Dumas, M. (1993). Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors. Lancet, 341, 265–8CrossRefGoogle ScholarPubMed
Couratier, P., Sindou, P., Esclaire, F. & Hugon, J. (1994). Neuroprotective effects of riluzole in ALS CSF toxicity. Neuroreport, 5, 1012–14CrossRefGoogle ScholarPubMed
Cullen, W. K., Wu, J. Q., Anwyl, R. & Rowan, M. J. (1996). beta-Amyloid produces a delayed NMDA receptor-dependent reduction in synaptic transmission in rat hippocampus. Neuroreport, 8, 87–92CrossRefGoogle ScholarPubMed
Curtis, D. R., Phillis, J. W. & Watkins, J. C. (1959). Chemical excitation of spinal neurones. Nature, 183, 611–12CrossRefGoogle ScholarPubMed
Das, S., Sasaki, Y. F., Rothe, T.et al. (1998). Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature, 393, 377–81CrossRefGoogle ScholarPubMed
Davis, G. C., Williams, A. C., Markey, S. P.et al. (1979). Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res., 1, 249–54CrossRefGoogle ScholarPubMed
Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S. & Snyder, S. H. (1991). Nitric oxide mediates glutamate neurotoxicity in primary cortical culture. Proc. Natl Acad. Sci., USA, 88, 6368–71CrossRefGoogle Scholar
DiDonato, S., Zeviani, M., Giovannini, P.et al. (1993). Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients. Neurology, 43, 2262–8CrossRefGoogle ScholarPubMed
Di Monte, D., Tetrud, J. W. & Langston, J. W. (1991). Blood lactate in Parkinson's disease and senescence. Biochem. Biophys. Res. Commun., 170, 483–9Google Scholar
Farber, N. B., Newcomer, J. W. & Olney, J. W. (1998). The glutamate synapse in neuropsychiatric disorders. Focus on schizophrenia and Alzheimer's disease. Prog. Brain Res., 116, 421–37CrossRefGoogle ScholarPubMed
Favaron, M., Manev, H., Siman, R.et al. (1990). Down regulation of protein kinase C protects cerebellar granule neurons in primary culture from glutamate-induced neuronal death. Proc. Natl Acad. Sci., USA, 87, 1983–7CrossRefGoogle ScholarPubMed
Fearnley, J. & Lees, A. (1991). Parkinson's disease: neuropathology. Brain, 114, 2283–301CrossRefGoogle Scholar
Fonnum, F. (1984). Glutamate: a neurotransmitter in mammalian brain. J. Neurochem., 42, 1–11CrossRefGoogle ScholarPubMed
Francis, P. T., Pangalos, M. N. & Bowen, D. M. (1992). Animal and drug modelling for Alzheimer synaptic pathology. Prog. Neurobiol., 39, 517–45CrossRefGoogle ScholarPubMed
Frandsen, A. & Schousboe, A. (1991). Dantrolene prevents glutamate cytotoxicity and Ca2+-release from intracellular stores in cultures cerebral cortical neurons. J. Neurochem., 56, 1075–8CrossRefGoogle ScholarPubMed
Frandsen, A. & Schousboe, A. (1992). Mobilization of dantrolene-sensitive intracellular calcium pools is involved in the cytotoxicity induced by quisqualate and N-methyl-D-asparate but not 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate and kainate in cultured cerebral cortical neurons. Proc. Natl Acad. Sci., USA, 89, 2590–4CrossRefGoogle Scholar
Gaudette, M., Hirano, M. & Siddique, T. (2000). Current status of SOD1 mutations in familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler. Other Motor Neuron Disord., 1, 83–9CrossRefGoogle ScholarPubMed
Giuffra, M. E., Sethy, V. H., Davis, T. L., Mouradian, M. M. & Chase, T. N. (1993). Milacemide therapy for Parkinson's disease. Movement Disord., 8, 47–50CrossRefGoogle ScholarPubMed
Giulian, D., Haverkamp, L. J., Li, J.et al. (1995). Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain. Neurochem. Int., 27, 119–37CrossRefGoogle ScholarPubMed
Goodwin, J. L., Uemura, E. & Cunnick, J. E. (1995). Microglial release of nitric oxide by the synergistic action of beta-amyloid and IFN-gamma. Brain Res., 692, 207–14CrossRefGoogle ScholarPubMed
Gossel, M., Schmidt, W. J., Loscher, W., Zajaczkowski, W. & Danysz, W. J. (1995). Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats. J. Neural Trans., 19, 27–39CrossRefGoogle Scholar
Greenamyre, J. T., Eller, R. V., Zhang, Z., Ovadia, A., Kurlan, R. & Gash, D. M. (1994). Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease. Ann. Neurol., 35, 655–61CrossRefGoogle ScholarPubMed
Greene, J. G. & Greenamyre, J. T. (1995). Manipulation of membrane potential modulates malonate-induced striatal excitotoxicity in vivo. J. Neurochem., 64, 2332–8CrossRefGoogle Scholar
Greene, J. G., Porter, R. H. P., Eller, R. V. & Greenamyre, J. T. (1993). Inhibition of succinate dehydrogenase by malonic acid produces an ‘excitotoxic’ lesion in rat striatum. J. Neurochem., 61, 1151–4CrossRefGoogle ScholarPubMed
Guerrini, L., Blasi, F. & Denis, D. (1995) Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro. Proc. Natl Acad. Sci., USA, 92, 9077–81CrossRefGoogle Scholar
Guyot, M. C., Palfi, S., Stutzmann, J. M., Maziere, M., Hantraye, P. & Brouillet, E. (1997). Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.Neuroscience, 81, 141–9CrossRefGoogle ScholarPubMed
Hansson, O., Petersen, A., Leist, M., Nicotera, P., Castilho, R. F. & Brundin, P. (1999). Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity.Proc. Natl Acad. Sci., USA, 96, 8727–32CrossRefGoogle ScholarPubMed
Harris, M. E., Wang, Y., Pedigo, N. W. Jr.., Butterfield, D. A. & Carney, J. M. (1996). Amyloid beta peptide (25–35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures.J. Neurochem., 67, 277–86CrossRefGoogle ScholarPubMed
Hattori, N., Tanaka, M., Ozawa, T. & Mizuno, Y. (1991). Immunohistochemical studies on complexes I, II, III and IV of mitochondria in Parkinson's disease. Ann. Neurol., 30, 563–71CrossRefGoogle ScholarPubMed
Hayashi, T. (1952). A physiological study of epileptic seizures following cortical stimulation in animals and its application to human clinics. Jpn J. Pharmacol., 3, 46–64Google ScholarPubMed
Hayashi, T. (1958). Inhibition and excitation due to γ-aminobutyric acid in the central nervous system. Nature, 182, 1076–7CrossRefGoogle ScholarPubMed
Henshaw, R., Jenkins, B. G., Schulz, J. B.et al. (1994). Malonate produces striatal lesions by indirect NMDA receptor activation. Brain Res., 647, 161–6CrossRefGoogle ScholarPubMed
Herb, A., Burnashev, N., Werner, P., Sakmann, B., Wisden, W. & Seeburg, P. H. (1992). The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron, 8, 775–85CrossRefGoogle ScholarPubMed
Herb, A., Higuchi, M., Sprengel, R. & Seeburg, P. H. (1996). Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proc. Natl Acad. Sci., USA, 93, 1875–80CrossRefGoogle ScholarPubMed
Hollmann, M. & Heinemann, S. (1994). Cloned glutamate receptors. Annu. Rev. Neurosci., 17, 31–108CrossRefGoogle ScholarPubMed
Hugon, J., Vallat, J. M., Spencer, P. S., Leboutet, M. J. & Barthe, D. (1989). Kainic acid induces early and delayed degenerative neuronal changes in rat spinal cord. Neurosci. Lett., 104, 258–62CrossRefGoogle ScholarPubMed
Ikonomidou, C. & Turski, L. (1996). Neurodegenerative disorders: clues from glutamate and energy metabolism. Crit. Rev. Neurobiol., 10, 239–63Google ScholarPubMed
Ikonomidou, C., Bosch, F., Miksa, M.et al. (1999). Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science, 283, 70–4CrossRefGoogle ScholarPubMed
Ikonomidou, C., Stefovska, V. & Turski, L. (2000). Neuronal death enhanced by N-methyl-D-aspartate antagonists. Proc. Natl Acad. Sci., USA, 97, 12885–90CrossRefGoogle ScholarPubMed
Ikonomidou, C., Qin, Y.-Q., Labruyere, J. & Olney, J. W. (1996). Motor neuron degeneration induced by excitotoxin agonists has features in common with those seen in the SOD-1 transgenic mouse model of amyotrophic lateral sclerosis.J. Neuropathol. Exp. Neurol., 55, 211–24CrossRefGoogle Scholar
Ischiropoulos, H., Zhu, L., Chen, J.et al. (1992). Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch. Biochem. Biophys., 298, 431–7CrossRefGoogle ScholarPubMed
Jain, K. K. (2000). Evaluation of memantine for neuroprotection in dementia. Expert Opin. Invest. Drugs., 9, 1397–406CrossRefGoogle ScholarPubMed
Janetzky, B., Hauck, S., Youdim, M. B.et al. (1994). Unaltered aconitase acitivity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson's disease. Neurosci. Lett., 169, 126–8CrossRefGoogle Scholar
Jones-H umble, S. A., Morgan, P. F. & Cooper, B. R. (1994). The novel anticonvulsant lamotrigine prevents dopamine depletion in C57 black mice in the MPTP animal model of Parkinson's disease. Life Sci., 54, 245–52CrossRefGoogle Scholar
Kasischke, K., Ludolph, A. C. & Riepe, M. W. (1996). NMDA-antagonist s reverse increased hypoxic tolerance by preceding chemical hypoxia. Neurosci. Lett., 214, 1–4CrossRefGoogle Scholar
Kieburtz, K., Feigin, A., McDermott, M.et al. (1996). A controlled trial of remacemide hydrochloride in Huntington's disease. Movement Disord., 11, 273–7CrossRefGoogle ScholarPubMed
Kilpatrick, G. J. & Tilbrook, G. S. (2002). Memantine. Merz. Curr. Opin. Investig. Drug., 3, 798–806Google ScholarPubMed
Klockgether, T., Turski, L., Honore, T.et al. (1991). The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann. Neurol., 30, 717–23CrossRefGoogle ScholarPubMed
Komuro, H. & Rakic, P. (1993). Modulation of neuronal migration by NMDA receptors. Science, 260, 95–7CrossRefGoogle ScholarPubMed
Krebs, H. A. (1935). Metabolism of amino acids. III Deamination of amino acids. Biochem. J., 29, 1520–44CrossRefGoogle Scholar
Lacomblez, L., Bensimon, G., Leigh, P. N., Guillet, P. & Meininger, V. (1996). Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet, 347, 1425–31CrossRefGoogle ScholarPubMed
Lai, E. C., Felice, K. J., Festoff, B. W.et al. (1997). Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF- I Study Group. Neurology, 49, 1621–30CrossRefGoogle Scholar
Lange, K. W., Loschmann, P. A., Sofic, E.et al. (1993). The competitive NMDA antagonists CPP protect substantia nigra neurons from MPTP-induced degeneration in primates. Naunyn-Schmiedebergs Arch. Pharmacol., 348, 586–92CrossRefGoogle Scholar
Langston, J. W., Ballard, P., Tetrud, J. W. & Irwin, I. (1983). Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science, 219, 979–80CrossRefGoogle ScholarPubMed
Lee, K. S., Frank, S., Vanderklish, P., Arai, A. & Lynch, G. (1991). Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc. Natl Acad. Sci., USA, 88, 7233–7CrossRefGoogle ScholarPubMed
Lees, G. J. (1993). The possible contribution of microglia and macrophages to delayed neuronal death after ischemia. J. Neurol. Sci., 114, 119–22CrossRefGoogle ScholarPubMed
Li, M., Ona, V. O., Guegan, C.et al. (2000). Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science, 288, 335–9CrossRefGoogle Scholar
Lucas, D. R. & Newhouse, J. P. (1957). The toxic effect of sodium-L-glutamate on the inner layers of the retina. Arch. Ophthalmol., 58, 193–201CrossRefGoogle ScholarPubMed
Luquin, M. R., Obeso, J. A., Laguna, J., Guillen, J. & Martineslage, J. M. (1993). The AMPA receptor antagonist NBQX does not alter the motor response induced by selective dopamine agonists in MPTP-treated monkeys. Eur. J. Pharmacol., 235, 297–300CrossRefGoogle Scholar
Malsch, U., Bother, K., Ramm, H. & Luhmann, R. (2001). Monotherapy of Parkinson's disease with budipine. A double blind comparison with amantadine. Fortsch. Neurol. Psychiatr., 69, 56–9Google ScholarPubMed
Manev, H., Favaron, M., Siman, R., Guidotti, A. & Costa, E. (1991). Glutamate neurotoxicity is independent of calpain I inhibition in primary cultures of cerebellar granule cells. J. Neurochem., 57, 1288–95CrossRefGoogle ScholarPubMed
Mann, V. M., Cooper, J. M., Krige, D., Daniel, S. E., Schapira, A. H. & Marsden, C. D. (1992). Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. Brain, 115, 333–42CrossRefGoogle ScholarPubMed
Matsuda, K., , Kamiya, Y., , Matsuda, S., & Yuzaki, M. (2002). Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res. Mol. Brain Res., 100, 43–52Google Scholar
Mattson, M. P. & Goodman, Y. (1995). Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. Brain Res., 676, 219–24CrossRefGoogle Scholar
McBain, C. J. & Mayer, M. L. (1994). N-methyl-D-aspartic acid receptor structure and function. Physiol. Rev., 74, 723–60CrossRefGoogle ScholarPubMed
McDonald, J. W. & Schoepp, D. D. (1992). The metabotropic excitatory amino acid receptors agonist 1S,3R-ACPD selectively potentiates N-methyl-D-asparate-induced brain injury. Eur. J. Pharmacol., 215, 353–4CrossRefGoogle Scholar
McGeer, P. L., Itagaki, S., Akiyama, H. & McGeer, E. G. (1989). Rate of cell death in parkinsonism indicates active neuropathological process. Ann. Neurol., 24, 574–6CrossRefGoogle Scholar
McMaster, O. G., Du, F., French, E. D. & Schwarcz, R. (1991). Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. Exp. Neurol., 113, 378–85CrossRefGoogle ScholarPubMed
Montastruc, J. L., Fabre, N., Rascol, O., Senard, J M. & Blin, O. (1994). N-methyl-D-aspartate (NMDA) antagonists and Parkinson's disease: a pilot study with dextromethorphan. Mov. Disord., 9, 242–3CrossRefGoogle ScholarPubMed
Montastruc, J. L., Rascol, O. & Senard, J. M. (1997). Glutamate antagonists and Parkinson's disease: a review of clinical data. Neurosci. Biobehav. Rev., 21, 477–80CrossRefGoogle ScholarPubMed
Monyer, H., Seeburg, P. H. & Wisden, W. (1991). Glutamate-operated channels: Developmentally early and mature forms arise by alternative splicing. Neuron, 6, 799–810CrossRefGoogle ScholarPubMed
Monyer, H., Sprengel, R., Schoepfer, R.et al. (1992). Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science, 256, 1217–21CrossRefGoogle ScholarPubMed
Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. (1994). Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron, 12, 529–40CrossRefGoogle ScholarPubMed
Murman, D. L., Giordani, B ., Mellow, A. M.et al. (1997). Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease. Neurology, 49, 153–61CrossRefGoogle ScholarPubMed
Nakagawa-Hattori, Y., Yoshino, H., Kondo, T., Mizuno, Y. & Horai, S. (1992). Is Parkinson's disease a mitochondrial disorder?J. Neurol. Sci., 107, 29–33CrossRefGoogle ScholarPubMed
Nagano, I., Wong, P. C. & Rothstein, J. D. (1996). Nitration of glutamate transporters in transgenic mice with a familial amyotrophic lateral sclerosis-linked SOD1 mutation. Ann. Neurol., 40, 542Google Scholar
Nakanishi, S. (1992). Molecular diversity of glutamate receptors and implications for brain function. Science, 258, 597–603CrossRefGoogle ScholarPubMed
Nathan, C. (1992). Nitric oxide as a secretory product of mammalian cells. FASEB J., 6, 3051–64CrossRefGoogle ScholarPubMed
Novelli, A., Reilly, J. A., Lysko, P. G. & Henneberry, R. C. (1988). Glutamate becomes neurotoxic via the N-methyl-D-asparate receptors when intracellular energy levels are reduced. Brain Res., 451, 205–12CrossRefGoogle Scholar
Olney, J. W. (1969). Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science, 164, 719–21CrossRefGoogle ScholarPubMed
Olney, J. W. (1971). Glutamate-induced neuronal necrosis in the infant mouse hypothalamus: an electron microscopic study. J. Neuropathol. Exp. Neurol., 30, 75–90CrossRefGoogle Scholar
Olney, J. W. & Ho, O. L. (1970). Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature, 227, 609–10CrossRefGoogle ScholarPubMed
Olney, J. W., Sharpe, L. G. & Feigin, R. D. (1972). Glutamate-induced brain damage in infant primates. J. Neuropathol. Exp. Neurol., 31, 464–88CrossRefGoogle ScholarPubMed
Olney, J. W., Wozniak, D. F. & Farber, N. B. (1997). Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. Arch. Neurol., 54, 1234–40CrossRefGoogle ScholarPubMed
Ossowska, K. (1994). The role of excitatory amino acids in experimental models of Parkinson's disease. J. Neural Trans., 8, 39–71CrossRefGoogle ScholarPubMed
Palfi, S. P., Ferrante, R. J., Brouillet, E . et al. (1996). Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease. J. Neurosci., 16, 3019–25CrossRefGoogle ScholarPubMed
Panov, A. V., Gutenkunst, C. A., Leavitt, B. R.et al. (2002). Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci., 5, 713–36CrossRefGoogle ScholarPubMed
Pantopoulos, H. & Hentze, M. W. (1995). Nitric oxide signaling to iron-regulatory protein: direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts. Proc. Natl Acad. Sci., USA, 92, 1267–71CrossRefGoogle ScholarPubMed
Papa, S. M., Engber, T. M., Boldry, R. C. & Chase, T. N. (1993). Opposite effects of NMDA and AMPA receptor blockade on catalepsy induced by dopamine receptor antagonists. Eur. J. Pharmacol., 232, 247–53CrossRefGoogle ScholarPubMed
Parkinson's Study Group (2000). A multicenter randomized controlled trial of remacemide hydrochloride as monotherapy for Parkinson's disease. Neurology, 54, 1583–8CrossRef
Parkinson's Study Group (2001). Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trial of remacemide in advanced Parkinson disease. Arch. Neurol., 58, 1660–8CrossRef
Parsons, C. G., Danysz, W. & Quack, G. (1998a). Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect., 11, 523–69CrossRefGoogle Scholar
Parsons, C. G., Hartmann, S. & Spielmanns, P. (1998b) Budipine is a low affinity, N-methyl-D-asparate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurones. Neuropharmacology, 37, 719–27CrossRefGoogle Scholar
Pasinelli, P., Houseweart, M. K., Brown, R. H. Jr. (2000). Caspase-1 and -3 are sequentially activated in motor neuron death in Cu, Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis. Proc. Natl Acad. Sci., USA, 97, 13901–6CrossRefGoogle ScholarPubMed
Perry, T. L., Hansen, S. & Jones, K. (1987). Brain glutamate deficiency in amyotrophic lateral sclerosis. Neurology, 37, 1845–8CrossRefGoogle ScholarPubMed
Pin, J. P.& Duvoisin, R. (1995). The metabotropic glutamate receptor: structure and function. Neuropharmacology, 34, 1–26CrossRefGoogle Scholar
Przuntek, H. & Muller, T. (1999). Clinical efficacy of budipine in Parkinson's disease. J. Neural Trans. Supp., 56, 75–82CrossRefGoogle ScholarPubMed
Przuntek, H., Bittkau, S., Bliesaht, H.et al. (2002) Budipine provides additional benefit in patients with Parkinsons disease receiving a stable optimum dopaminergic drug regimen. Arch. Neurol., 59, 803–6CrossRefGoogle ScholarPubMed
Radi, R., Beckman, J. S., Bush, K. M. & Freeman, B. A. (1991a). Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys., 288, 484–7CrossRefGoogle Scholar
Radi, R., Beckman, J. S., Bush, K. M. & Freeman, B. A. (1991b). Peroxynitrite oxidation of sulfhydryls. J. Biol. Chem., 266, 4244–50Google Scholar
Rabey, J. M., Nissipeanu, P. & Korczyn, A. D. (1992). Efficacy of memantine, an NMDA receptor antagonist, in the treatment of Parkinson's disease. J. Neural Trans., 4, 277–82CrossRefGoogle ScholarPubMed
Riepe, M. & Ludolph, A. C. (1997). Chemical preconditioning: a cytoprotective strategy. Mol. Cell Biochem., 174, 249–54CrossRefGoogle ScholarPubMed
Riepe, H. W., Hori, N., Ludolph, A. C. & Carpenter, D. O. (1995). Failure of neuronal ion exchange, not potentiated excitation, causes excitotoxicity after inhibition of oxidative phosphorylation. Neuroscience, 64, 91–7CrossRefGoogle Scholar
Rordorf, G., Uemura, Y. & Bonventre, J. V. (1991) Characterization of phospholipase A2 (PLA2) activity in gerbil brain: enhanced activities of cytosolic, mitochondrial, and microsomal forms after ischemia and reperfusion. J. Neurosci., 11, 1829–36CrossRefGoogle ScholarPubMed
Rothman, S. M. (1985). The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J. Neurosci., 5, 1483–9CrossRefGoogle ScholarPubMed
Rothman, S. M., Yamada, K. A. & Lancaster, N. L. (1993). Nordihydroguaiaretic acid attenuates NMDA neurotoxicity-action beyond the receptor. Neuropharmacology, 32, 1279–88CrossRefGoogle ScholarPubMed
Rothstein, J. D., Martin, L. J. & Kuncl, R. W. (1992). Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N. Engl. J. Med., 326, 1464–8CrossRefGoogle ScholarPubMed
Rothstein, J. D., Kammen, M., Levey, A. I., Martin, L. J. & Kuncl, R. W. (1995). Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol., 38, 73–84CrossRefGoogle ScholarPubMed
Samples, S. D. & Dubinsky, J. M. (1993). Aurintricarboxylic acid protects hippocampal neurons from glutamate excitotoxicity in vitro. J. Neurochem., 61, 382–5CrossRefGoogle ScholarPubMed
Santiago, M., Venero, J. L., Machado, A. & Cano, J. (1992). In vivo protection of striatum from MPP+ neurotoxicity by N-methyl-D-asparate antagonists. Brain Res., 586, 203–7CrossRefGoogle Scholar
Sawa, A., Wiegand, G. W., Cooper, J.et al. (1999). Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat. Med., 5, 1194–8CrossRefGoogle ScholarPubMed
Schapira, A. H., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P. & Marsden, C. D. (1990a). Mitochondrial complex I deficiency in Parkinson's disease. J. Neurochem., 54, 823–7CrossRefGoogle Scholar
Schapira, A. H., Mann, V. M., Cooper, J. M.et al. (1990b). Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease. J. Neurochem., 55, 2142–5CrossRefGoogle Scholar
Schilling, G ., Becher, M. W., Sharp, A. H.et al. (1999). Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Molec. Genet., 8, 397–407CrossRefGoogle ScholarPubMed
Schmidt, W. J. & Kretschmer, B. D. (1997). Behavioural pharmacology of glutamate receptors in the basal ganglia. Neurosci. Biobehav. Res., 21, 381–92CrossRefGoogle ScholarPubMed
Schoepp, D. D., Tizzano, J. P., Wright, R. A. & Fix, A. S. (1995). Reversible and irreversible neuronal injury induced by intrahippocampal infusion of the mGluR agonist 1S,3R-ACPD in the rat. Neurodegeneration, 4, 71–80CrossRefGoogle ScholarPubMed
Schulz, J. B., Henshaw, D. R., Jenkins, B. G.et al. (1994). 3-Acetylpyridine produces age-dependent neuronal lesions by an excitotoxic and free radical mediated mechanim. J. Cereb. Blood Flow Metab., 14, 1024–9CrossRefGoogle Scholar
Schulz, J. B., Matthews, R. T., Muqit, M. M., Browne, S. E. & Beal, M. F. (1995). Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP induced neurotoxicity in mice. J. Neurochem., 64, 936–9CrossRefGoogle ScholarPubMed
Schwab, R. S., England, , , A. C., Poskranzer, D. C. & Young, R. R. (1969). Amantadine in the treatment of Parkinson's disease. J. Ann. Med. Assn., 208, 1168–70CrossRefGoogle ScholarPubMed
Schwarcz, R. & Kohler, C. (1983). Differential vulnerability of central neurons of the rat to quinolinic acid. Neurosci. Lett., 38, 85–90CrossRefGoogle ScholarPubMed
Schwarcz, R., Whetsell, W. O. & Mangano, R. M. (1983). Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science, 219, 316–18CrossRefGoogle ScholarPubMed
Schwarcz, R., Okuno, E., White, R. J., Bird, E. D. & Whetsell, W. O. Jr. (1988). 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Proc. Natl Acad. Sci., USA, 85, 4079–81CrossRefGoogle Scholar
Selkoe, D. J. (1999). Translating cell biology into therapeutic advances in Alzheimer's disease. Nature Suppl., 399, A23–31Google ScholarPubMed
Shaw, P. J., Forrest, V., Ince, P. G., Richardson, J. P. & Wastell, H. J. (1995). Studies on cellular free radical protection mechanisms in the anterior horn from patients with amyotrophic lateral sclerosis. Neurodegeneration, 4, 209–16CrossRefGoogle ScholarPubMed
Spencer, P. S. (1987). Guam ALS/parkinsonis m-dementia: a long-latency neurotoxic disorder caused by ‘slow toxin(s)’ in food?Can. J. Neurol. Sci., 14(3Suppl), 347–57CrossRefGoogle Scholar
Spencer, P. S., Roy, D. N., Ludolph, A., Hugon, J., Dwivedi, M. P. & Schaumburg, H. H. (1986). Lathyrism: evidence for the role of the neuroexcitatory amino acid BOAA. Lancet, ii, 1066–7CrossRefGoogle Scholar
Spencer, P. S., Kisby, G. E., Ross, S. M.et al. (1993). Guam ALS-PDC: possible causes. Science, 262, 825–6CrossRefGoogle ScholarPubMed
Spieker, S., Eisebitt, R., Breit, S.et al. (1999). Tremorlytic activity of budipine in Parkinson's disease. Clin. Neuropharmacol., 22, 115–19CrossRefGoogle ScholarPubMed
Srivastava, R., Brouillet, E., Beal, M. F., Storey, E. & Hyman, B. T. (1993). Blockade of 1-methyl-4-phenylpyridinium ion (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment. Neurobiol. Agin., 14, 295–301CrossRefGoogle ScholarPubMed
Taylor, D. J., Krige, D., Barnes, P. R.et al. (1994). A 31P magnetic resonance spectroscopy study of mitochondrial function in skeletal muscle of patients with Parkinson's disease. J. Neurol. Sci., 125, 77–81CrossRefGoogle ScholarPubMed
Terro, F., Lasort, M., Vlader, F., Ludolph, A. & Hugon, J. (1996). Antioxidant drugs block in vitro the neurotoxicity of CSF from patients with amyotrophic lateral sclerosis. Neuroreport, 7, 1970–2Google ScholarPubMed
Terry, R. D. & Davies, P. (1980). Dementia of the Alzheimer type. Ann. Rev. Neurosci., 3, 77–95CrossRefGoogle ScholarPubMed
The BDNF Study Group. (1999). A controlled trial of recombinant methionyl human BDNF in ALS: (Phase III). Neurology, 52, 1427–33CrossRef
Turski, L., Bressler, K., Rettig, K. J., Loschmann, P. A. & Wachtel, H. (1991). Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature, 349, 414–18CrossRefGoogle ScholarPubMed
Tymianski, M., Wallace, M. C., Spigelman, I.et al. (1993). Cell-permeant Ca2+-chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo. Neuron, 11, 221–35CrossRefGoogle ScholarPubMed
Uitti, R. J., Rajput, A. H., Ahlskog, J. E.et al. (1996). Amantadine treatment is an independent predictor of improved survival in Parkinson's disease. Neurology, 46, 1551–6CrossRefGoogle ScholarPubMed
Urbanska, E., Ikonomidou, C., Sieklucka, M. & Turski, W. A. (1991). Aminooxyacetic acid produces excitotoxic lesions in the rat striatum. Synapse, 9, 129–35CrossRefGoogle ScholarPubMed
Verhagen Metman, L., Del Dotto, P., Blanchet, P. J., Munckhof, P. & Chase, T. N. (1998) Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Amino Acids, 14, 75–82CrossRefGoogle ScholarPubMed
Vukosavic, S., Stefanis, L., Jackson-Lewis, V.et al. (2000). Delaying caspase activation by Bcl-2: a clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurosci., 20, 9119–25CrossRefGoogle Scholar
Wachtel, H., Kunow, M. & Loschmann, P. A. (1992). NBQX (6-nitro-sulfamoyl-benzo-quinoxal ine-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. Neurosci. Lett., 142, 179–82CrossRefGoogle Scholar
Williams, T. L., Day, N. C. Kamboj., Ince, P. G. & Shaw, P. J. (1997). Calcium-permeable alpha-amino-3-hydroxy-5-me thyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Ann. Neurol., 35, 200–7CrossRefGoogle Scholar
Winblad, B. & Poritis, N. (1999) Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int. J. Geriatr. Psychiatr., 14, 135–463.0.CO;2-0>CrossRefGoogle Scholar
Wozniak, D. F., Dikranian, K., Ishimaru, M. J.et al. (1998). Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801: potential relevance to Alzheimer's disease. Neurobiol. Dis., 5, 305–22CrossRefGoogle ScholarPubMed
Wüllner, U., Young, A. B., Penney, J. B. & Beal, M. F. (1994). 3-Nitropropionic acid toxicity in the striatum. J. Neurochem., 63, 1772–81CrossRefGoogle ScholarPubMed
Young, A. B. (1990). What's the excitement about excitatory amino acids in amyotrophic lateral sclerosis?Ann. Neurol., 28, 9–11CrossRefGoogle ScholarPubMed
Zadow, B. & Schmidt, W. J. (1994). The AMPA antagonists NBQX and GYKI 52466 do not counteract neuroleptic-induced catalepsy. Naunyn Schmied Arch. Pharmacol., 349, 61–5CrossRefGoogle Scholar
Zeevalk, G. D. & Nicklas, W. J. (1991). Mechanisms underlying initiation of excitotoxicity associated with metabolic inhibition. J. Pharmacol. Exp. Ther., 257, 870–8Google ScholarPubMed
Zhang, J., Dawson, V. L., Dawson, T. M. & Snyder, S. H. (1994). Nitric oxide activation of poly (ADP-ribose)synt hetase in neurotoxicity. Science, 263, 687–9CrossRefGoogle Scholar
Zipp, F., Baas, H. & Fischer, P. A. (1993). Lamotrigine – antiparkinsonian activity by blockade of glutamate release?J. Neural Transm., 5, 67–75CrossRefGoogle ScholarPubMed
Zipp, F., Burklin, F., Stecker, K., Baas, H. & Fischer, P. A. (1995). Lamotrigine in Parkinson's disease – a double blind study. J. Neural Trans., 10, 199–206CrossRefGoogle ScholarPubMed
Zuddas, A., Oberto, G., Vaglini, F., Fascetti, F., Fornai, F. & Corsini, G. U. (1992). MK-801 prevents 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced parkinsonism in primates. J. Neurochem., 59, 733–9CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×