Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Stand der klinischen Forschung bei den NMDA-Rezeptorantagonisten im Neugeborenen- und Kindesalter

  • Conference paper
Oxidativer Stress in der Kinderheilkunde

  • 27 Accesses

Zusammenfassung

Glutamat, Aspartat und weitere Aminosäuren sind die Agonisten exzitatorischer Synapsen des zentralen Nervensystems und werden an ca. 40% aller Synapsen präsynaptisch freigesetzt (Mattson et al. 1993; McDonald u. Johnston 1990; Mikkelsen et al. 1993; Lipton u. Rosenberg 1994). Während extrazelluläre Glutamatkonzentrationen von 0,3–0,6 μM physiologisch sind, liegt die neurotoxische Konzentration mit 2–5 μM nur wenig darüber. Die parenchymatöse, intrazelluläre Glutamatkonzentration ist mit 3–10 mM 10 ooofach höher als die extrazelluläre (Coyle u. Puttfarcken 1993; Lipton u. Rosenberg 1994). Für die Erhaltung dieses Glutamatgra-dienten sind hochaffine, energieabhängige Transportsysteme zuständig.

Prof. Dr. Franz-Josef Schulte, Hamburg, zu seinem 65. Geburtstag.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  • Albers GW, Atkinson R, Kelley R, Rosenbaum DM (1994) Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with an acute stroke. Neurology 44 (Suppl 2, Abstr):A270

    Google Scholar 

  • Barks JD, Silverstein FS, Sims K et al. (1988) Glutamate recognition sites in human fetal brain. Neurosci Lett 84:131–136

    Article  PubMed  CAS  Google Scholar 

  • Bern JL, Peck R (1992) Dextromethorphan. An overview of safety issues. Drug Saf 7:190–199

    Article  Google Scholar 

  • Bensimon G, Lacomblez L, Meininger V, ALS/Riluzole Study Group (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 330:585–591

    Article  PubMed  CAS  Google Scholar 

  • Borlak JT, Harsany V, Schneble H, Haegele KD (1994) pNAT and CYP2D6 gene polymorphism in epileptic patients. Biochem Pharmacol 48:1717–1720

    Article  PubMed  CAS  Google Scholar 

  • Brockmöller J, Roots I (1994) Assessment of liver metabolic function. Clinical implications. Clin Pharmacokinet 27:216–248

    Article  PubMed  Google Scholar 

  • Carpenter CL, Marks SS, Watson DL, Greenberg DA (1988) Dextromethorphan and dextrorphan as calcium channel antagonists. Brain Res 439:372–375

    Article  PubMed  CAS  Google Scholar 

  • Clemens JA, Saunders RD, Ho PP et al. (1993) The antioxidant LY231617 reduces global ischemic neuronal injury in rats. Stroke 24:716–723

    Article  PubMed  CAS  Google Scholar 

  • Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695

    Article  PubMed  CAS  Google Scholar 

  • Dirnagl U (1993) Cerebral ischemia: The microcirculation as trigger and target. In: Kogure K, Hossmann K-A, Siesjö BK (eds) Progress in brain research, vol 96. Elsevier, North-Holland Amsterdam, pp 49–65

    Google Scholar 

  • During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in conscious human brain. Lancet 341:1607–1610

    Article  PubMed  CAS  Google Scholar 

  • Faden AI, Demediuk P, Panter SS, Vink R (1989) The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:798–800

    Article  PubMed  CAS  Google Scholar 

  • Ginsberg MD (1993) Emerging strategies for the treatment of ischemic brain injury. In: Waxman SG (ed) Molecular and cellular approaches to the treatment of neurological disease. Raven Press, New York, pp 207–237

    Google Scholar 

  • Greenamyre T, Penney JB, Young AB et al. (1987) Evidence for transient perinatal glutamatergic innervation of globus pallidus. J Neurosci 7:1022–1030

    PubMed  CAS  Google Scholar 

  • Hall ED, Andrus PK, Althaus JS, VonVoigtlander PF (1993) Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain. J Neurosci Res 34:107–112

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JMC (1989) Free radicals in biology and medicine, 2nd edn. Clarendon Press, Oxford

    Google Scholar 

  • Hamosh A, McDonald JW, Valle D et al. (1992) Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant. J Pediatr 121:131–135

    Article  PubMed  CAS  Google Scholar 

  • Hattori H, Wasterlain CG (1990) Excitatory amino acids in the developing brain: Ontogeny, plasticity, and excitotoxicity. Pediatr Neurol 6:219–228

    Article  PubMed  CAS  Google Scholar 

  • Hoffman DJ, McGowan JE, Marro PJ et al. (1994) Hypoxia-induced modification of the N-methyl-D-aspartate receptor in the brain of the newborn piglet. Neurosci Lett 167:156–160

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Maron C, Heinemann S (1994) N-Glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13:1331–1343

    Article  PubMed  CAS  Google Scholar 

  • Holmes GL, Werner S, Liu Z et al. (1994) Adverse effects of excitatory amino antagonists on the developing brain. Ann Neurol 36 (Abstr):494

    Article  Google Scholar 

  • Ikonomidou C, Mosinger JL, Salles KS et al. (1989) Sensitivity of the developing rat brain to hypobaric/ischemic damage parallels sensitivity to N-methyl-D-aspartate neurotoxicity. J Neurosci 9:2809–2818

    PubMed  CAS  Google Scholar 

  • Johnson M, Perry EK, Ince PG et al. (1993) Autoradiographic comparison of the distribution of [3H]MK801 and [3H]CNQX in the human cerebellum during development and aging. Brain Res 615:259–266

    Article  PubMed  CAS  Google Scholar 

  • Kato S, Negishi K, Mawatari K, Kuo C-H (1992) A mechanism for glutamate toxicity in the C6 glioma cells involving inhibition of cystine uptake leading to glutathione depletion. Neuroscience 48:903–914

    Article  PubMed  CAS  Google Scholar 

  • Kornhuber J, Mack-Burkhardt F, Konradi C et al. (1989) Effect of antemor-tem and postmortem factors on [3H]MK-801 binding in the human brain: Transient elevation during early childhood. Life Sci 45:745–749

    Article  PubMed  CAS  Google Scholar 

  • Kupsky WJ, Drozd MA, Barlow CF (1995) Selective injury of the globus pallidus in children with post-cardiac surgery choreic syndrome. Dev Med Child Neurol 37:135–144

    Article  PubMed  CAS  Google Scholar 

  • Kutsuwada T, Kashiwabuchi N, Mori H et al. (1992) Molecular diversity of the NMDA receptor channel. Nature 358:36–41

    Article  PubMed  CAS  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622

    Article  PubMed  CAS  Google Scholar 

  • Lipton SA, Chol Y-B, Pan Z-H et al. (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632

    Article  PubMed  CAS  Google Scholar 

  • Makar TK, Nedergaard M, Preuss A et al. (1994) Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: Evidence that astrocytes play an important role in antioxidative processes in the brain. J Neurochem 62:45–53

    Article  PubMed  CAS  Google Scholar 

  • Manchester KS, Jensen FE, Warach S, Lipton SA (1993) Chronic administration of nitroglycerin decreases cerebral infarct size. Neurology 43 (Abstr):A365

    Google Scholar 

  • Manev H, Favaron M, Candeo P et al. (1993) Macrolide antibiotics protect neurons in culture against the N-methyl-D-aspartate (NMDA) receptor-mediated toxicity of glutamate. Brain Res 624:331–335

    Article  PubMed  CAS  Google Scholar 

  • Marret S, Gressens P, Gadisseux J-F, Evrard P (1995) Prevention by magnesium of excitotoxic neuronal death in the developing brain. An animal model for clinical intervention studies. Dev Med Child Neurol — in press

    Google Scholar 

  • Mattson MP, Kumar KN, Wang H et al. (1993) Basic FGF regulates the expression of a functional 71 kDa NMDA receptor protein that mediates calcium influx and neurotoxicity in hippocampal neurons. J Neurosci 13:4575–4588

    PubMed  CAS  Google Scholar 

  • McDonald JW, Johnston MV (1990) Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res Rev 15:41–70

    Article  PubMed  Google Scholar 

  • McDonald JW, Silverstein FS, Johnston MV (1990) MK-801 pretreatment enhances N-methyl-D-aspartate-mediated brain injury and increases brain N-methyl-D-aspartate recognition site binding in rats. Neuroscience 38:103–113

    Article  PubMed  CAS  Google Scholar 

  • Meldrum B (1993) Amino acids as dietary excitotoxins: A contribution to understanding neurodegenerative disorders. Brain Res Rev 18:293–314

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen JD, Larsen PJ, Ebling FJP (1993) Distribution of N-methyl-D-aspartate (NMDA) receptor mRNAs in the rat suprachiasmatic nucleus. Brain Res 632:329–333

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto M, Murphy TH, Schnaar RL, Coyle JT (1989) Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J Pharmacol Exp Ther 250:1132–1140

    PubMed  CAS  Google Scholar 

  • Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    Article  PubMed  CAS  Google Scholar 

  • Monyer H, Sprengel R, Schoepfer R et al. (1992) Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science 256:1217–1221

    Article  PubMed  CAS  Google Scholar 

  • Monyer H, Burnashev N, Laurie DJ et al. (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540

    Article  PubMed  CAS  Google Scholar 

  • Moody DM, Bell MA, Challa VR et al. (1990) Brain microemboli during cardiac surgery or aortography. Ann Neurol 28:477–486

    Article  PubMed  CAS  Google Scholar 

  • Moriyoshi K, Masu M, Ishii T et al. (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354:31–37

    Article  PubMed  CAS  Google Scholar 

  • Murphy TH, Schnaar RL, Coyle JT (1990) Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J 4:1624–1633

    PubMed  CAS  Google Scholar 

  • Murphy TH, De Long MJ, Coyle JT (1991) Enhanced NAD(P)H:quinone reductase activity prevents glutamate toxicity produced by oxidative stress. J Neurochem 56:990–995

    Article  PubMed  CAS  Google Scholar 

  • Newburger JW, Jonas RA, Wernovsky G et al. (1993) A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant surgery. N Engl J Med 329:1057–1064

    Article  PubMed  CAS  Google Scholar 

  • Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ (1993) Vulnerability of Oligodendroglia to glutamate: Pharmacology, mechanisms, and prevention. J Neurosci 13:1441–1453

    PubMed  CAS  Google Scholar 

  • Olney JW (1993) Role of excitotoxins in developmental neuropathology. APMIS 101 (Suppl 40):103–112

    Google Scholar 

  • Olney JW, Labruyere J, Price MT (1989) Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362

    Article  PubMed  CAS  Google Scholar 

  • 0ye I, Paulsen O, Maurset A (1992) Effects of ketamine on sensory perception: Evidence for a role of N-emthyl-D-aspartate receptors. J Pharmacol Exp Ther 260:1209–1213

    PubMed  CAS  Google Scholar 

  • Piggott MA, Perry EK, Perry RH, Court JA (1992) [3H]MK-801 binding to the NMDA receptor complex, and its modulation in human frontal cortex during development and aging. Brain Res 588:277–286

    Article  PubMed  CAS  Google Scholar 

  • Plessis AJ du, Treves ST, Hickey PR et al. (1994) Regional cerebral perfusion abnormalities after cardiac operations. Single photon emission computed tomography (SPECT) findings in children with postoperative movement disorders. J Thorac Cardiovasc Surg 107:1036–1043

    PubMed  Google Scholar 

  • Ratan RR, Murphy TH, Baraban JM (1994) Oxidative stress induces apopto-sis in embryonic cortical neurons. J Neurochem 62:376–379

    Article  PubMed  CAS  Google Scholar 

  • Redmond JM, Gillinov AM, Blue ME et al. (1993) The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest. Surgery 114:324–333

    PubMed  CAS  Google Scholar 

  • Redmond JM, Gillinov AM, Zehr KJ et al. (1994) Glutamate excitotoxicity: A mechanism of neurologic injury associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg 107:776–787

    PubMed  CAS  Google Scholar 

  • Rod MR, Auer RN (1992) Combination therapy with nimodipine and dizo-cilpine in a rat model of transient forebrain ischemia. Stroke 23:725–732

    Article  PubMed  CAS  Google Scholar 

  • Rogers SW, Andrews PI, Gahring LC et al. (1994) Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science 265:648–651

    Article  PubMed  CAS  Google Scholar 

  • Rokkas CK, Helfrich LR jr, Lobner DC et al. (1994) Dextrorphan inhibits the release of excitatory amino acids during spinal cord ischemia. Ann Thorac Surg 58:312–320

    Article  PubMed  CAS  Google Scholar 

  • Roots I, Brockmöller J, Drakoulis N, Loddenkemper S (1992) Mutant genes of cytochrome P-450IID6, glutathione S-transferase class Mu, and aryla-mine N-acetyltransferase in lung cancer patients. Clin Investig 70:307–319

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg PA, Amin S, Leitner M (1992) Glutamate uptake disguises neurotoxic potency of glutamate agonists in cerebral cortex in dissociated cell culture. J Neurosci 12:56–61

    PubMed  CAS  Google Scholar 

  • Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H, Mishina M (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit. Nature 373:151–155

    Article  PubMed  CAS  Google Scholar 

  • Schmitt B, Steinmann B, Gitzelmann R et al. (1993) Nonketotic hyperglycinemia: Clinical and electrophysiologic effects of dextromethorphan, an antagonist of the NMDA receptor. Neurology 43:421–424

    PubMed  CAS  Google Scholar 

  • Schmitt B, Netzer R, Fanconi S et al. (1994) Drug refractory epilepsy in brain damage: Effect of dextromethorphan on EEG in four patients. J Neurol Neurosurg Psychiatry 57:333–339

    Article  PubMed  CAS  Google Scholar 

  • Sharkey J, Butcher SP (1994) Immunophilins mediate the neuroprotective effects of FK506 in fokal cerebral ischaemia. Nature 371:336–339

    Article  PubMed  CAS  Google Scholar 

  • Sheng M, Cummings J, Roldan LA et al. (1994) Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368:144–147

    Article  PubMed  CAS  Google Scholar 

  • Söderberg M, Edlund C, Kristensson K, Dallner G (1990) Lipid compositions of different regions of the human brain during aging. J Neurochem 54:415–423

    Article  PubMed  Google Scholar 

  • Stamler JS (1994) Redox signaling: Nitrosylation and related target interactions of nitric oxide. Cell 78:931–936

    Article  PubMed  CAS  Google Scholar 

  • Steinberg GK, Bell T (1991) Clinical dose-escalation safety study of the NMDA antagonist, dextromethorphan in neurosurgical patients. Stroke 22 (Abstr):141

    Google Scholar 

  • Steinberg GK, Kunis D, DeLaPaz R, Poljak A (1993) Neuroprotection following focal cerebral ischaemia with the NMDA antagonist dextromethorphan, has a favourable dose response profile. Neurol Res 15:174–180

    PubMed  CAS  Google Scholar 

  • Stern-Bach Y, Bettler B, Hartley M et al. (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13:1345–1357

    Article  PubMed  CAS  Google Scholar 

  • The American Nimodipine Study Group 1992 (1992) Clinical trial of Nimodipine in acute ischemic stroke. Stroke 23:3–8

    Article  Google Scholar 

  • Trube G, Netzer R (1994) Dextromethorphan: Cellular effects reducing neuronal hyperactivity. Epilepsia 35 (Suppl 5):S62–S67

    Article  PubMed  Google Scholar 

  • Volpe JJ (1989) Current concepts of brain injury in the premature infant. Am J Roentgenol 153:243–251

    CAS  Google Scholar 

  • Volterra A, Trotti D, Tromba C et al. (1994) Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes. J Neurosci 14:2924–2932

    PubMed  CAS  Google Scholar 

  • Wafford KA, Bain CJ, Le Bourdelles B et al. (1993) Preferential co-assembly of recombinant NMDA receptors composed of three different subunits. Neuroreport 4:1347–1349

    Article  PubMed  CAS  Google Scholar 

  • Wahlestedt C, Golanov E, Yamamoto S et al. (1993) Antisense oligodeoxy-nucleotides to NMDA-R1 receptor channel protect cortical neurons from excitotoxicity and reduce focal ischaemic infarctions. Nature 363:260–263

    Article  PubMed  CAS  Google Scholar 

  • Wong PC, Barlow CF, Hickey PR et al. (1992) Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease. Circulation 86 (Suppl II):II-188-II-126

    Google Scholar 

  • Yue T-L, Barone FC, Gu J-L, Feuerstein GZ (1993) Brain α-tokopherol levels are not altered following ischemia/reperfusion-induced cerebral injury in rats and gerbils. Brain Res 610:53–56

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Dawson VL, Dawson TM, Snyder SH (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263:687–698

    Article  PubMed  CAS  Google Scholar 

  • Zhang J-R, Andrus PK, Hall ED (1993) Age-related regional changes in hydroxyl radical stress and antioxidants in gerbil brain. J Neurochem 61:1640–1647

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. C. Hübner
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrum der Kinderheilkunde, Klinikum der Universität Frankfurt, Theodor-Stern-Kai 7, 60559, Frankfurt/Main, Deutschland

    Hansjosef Böhles

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hübner, C. (1995). Stand der klinischen Forschung bei den NMDA-Rezeptorantagonisten im Neugeborenen- und Kindesalter. In: Böhles, H. (eds) Oxidativer Stress in der Kinderheilkunde. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79748-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-79748-4_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-59256-3

  • Online ISBN: 978-3-642-79748-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation