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European Journal of Pediatrics

, Volume 154, Issue 8, pp 649–653 | Cite as

Ketamine and strychnine treatment of an infant with nonketotic hyperglycinaemia

  • H. Tegtmeyer-Metzdorf
  • B. Roth
  • M. Günther
  • M. Theisohn
  • U. Heinemann
  • H. A. Adams
  • G. Sticht
Original Paper

Abstract

Abstract

Non-ketotic hyperglycinaemia (NKH) is a severe seizure disorder associated with high glycine levels. Glycine is a major inhibitory neurotransmitter in the CNS, but has also modulating effects at one of the glutamate receptors, the N-methyl-d-aspartate-(NMDA) receptor. Based on this knowledge we treated a female newborn suffering from severe NKH with the NMDA receptor blocker ketamine in association with strychnine and magnesium supplementation. This treatment led to cessation of seizures, reappearance of swallowing and sucking and improved the neurological status. Some pharmacokinetic data of strychnine and ketamine in the infant are given.

Conclusion

Ketamine in combination with strychnine may be beneficial in non-ketotic hyperglycinaemia.

Key words

Excitotocicity Ketamine N-methyl-d-aspartate receptor Strychnine Non ketotic hyperglycinaemia 

Abbreviations

GABA

gamma-amino-butyric acid

HPLC

high performance liquid chromatography

NKH

non-ketotic hyperglycinaemia

NMDA

N-methyl-d-aspartate

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References

  1. 1.
    Adams HA, Weber B, Bachmann MB, Grünberg T, Hempelmann G (1991) Die Bestimmung von Ketamin und Midazolam mittels Hochdruck-Flüssigkeitschromatographie und UV-Detektion (HPLC/UV). Fortschr Anästh Notf 5: 13 [Suppl 1] A12Google Scholar
  2. 2.
    Albers GW, Goldberg MP, Choi DW (1989) N-methyl-d-aspartate antagonists: Ready for clinical trial in brain ischemia? Ann Neurol 25: 398–403PubMedGoogle Scholar
  3. 3.
    Albrecht D (1991) Ontogenetische Aspekte der Kaliumregulation und der Epileptogenizität im Hippocampus der Ratte. Inauguraldissertation der Math.-Nat. Fakultät der Universität zu KölnGoogle Scholar
  4. 4.
    Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics ketamine and phencyclidine, selectively reduce excitations of central mammalian neurons by N-methyl-aspartate. Br J Pharmacol 79: 565–575PubMedGoogle Scholar
  5. 5.
    Aukett A, Braithwaite RA, Green A (1986) Failure of early diazepam treatment in a neonate with non-ketotic hyperglycinaemia. J Inherited Metab Dis 9: 268–271Google Scholar
  6. 6.
    Bain MD, Jones M, Sousa C de, Lee T, Chaimers RA (1992) Treatment of an infant with non-ketotic hyperglycinemia. 30th Ann. Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM); September 8th–11th, Leuven; Abstracts of Free Communications p 34Google Scholar
  7. 7.
    Chapman AG, Meldrum BS (1989) Non-competitive N-methyl-d-asparate antagonists protect against sound-induced seizures in DBA/2 mice. Eur Pharmacol 166: 201–211Google Scholar
  8. 8.
    Church J, Zeman S, Lodge D (1988) The neuroprotective action of ketamine and MK-801 after transient cerebral ischemia in rats. Anesthesiology 69: 702–709PubMedGoogle Scholar
  9. 9.
    Grant IS, Nimmo WS, Clements JA (1981) Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Br J Anaesth 53: 805–810PubMedGoogle Scholar
  10. 10.
    Hamosh A, McDonald JW, Valle D, Francomano CA, Niedermeyer E, Johnston MV (1992) Dextro-methorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in an infant. J Pediatr 121: 131–135PubMedGoogle Scholar
  11. 11.
    Hauschild F (1973) Pharmakologie und Grundlagen der Toxikologie. Leipzig: Thieme-Verlag 125–126Google Scholar
  12. 12.
    Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325: 529–531PubMedGoogle Scholar
  13. 13.
    Lehmann J, Hutchson AJ, McPherson SE, Mondadori C, Schmutz M, et al (1988) CGS 1975, a selective and competitive N-methyl-d-aspartate-type excitatory amino acid receptor antagonist. J Pharmacol Exp Ther 246: 65–72PubMedGoogle Scholar
  14. 14.
    MacDermott KD, Nelson W, Soutter V, Towne D, Schulman JD (1981) Glycine and benzoate conjugation and glycine acyltransferase activity in the developing and adult rat: Possible relationships in nonketotic hyperglycinemia. Dev Pharmacol Ther 3: 150–159PubMedGoogle Scholar
  15. 15.
    Matalon R, Michals K, Naidu S, Hughes J (1982) Treatment of nonketotic hyperglycinemia with diazepam, choline and folic acid. J Inherited Metab Dis 5S: 3–5Google Scholar
  16. 16.
    Matalon R, Naidu S, Hughes JR, Michals K (1983) Nonketotic hyperglycinemia: A treatment with diazepam — a competitor for glycine receptors. Pediatrics 71: 581–584PubMedGoogle Scholar
  17. 17.
    McDonald JW, Silverstein FS, Johnston MV (1988) Neurotoxicity of N-methyl-d-aspartate is markedly enhanced in developing rat central nervous system. Brain Res 459: 200–203PubMedGoogle Scholar
  18. 18.
    McDonald JW, Johnston MV (1990) Nonketotic hyperglycinemia: pathophysiological role of NMDA-type excitatory amino acid receptors. Ann Neurol 27: 449–450PubMedGoogle Scholar
  19. 19.
    Meldrum BS, Evans MC, Swan JH, Simon RP (1987) Protection against hypoxic/ischaemic brain damage with excitatory amino acid antagonists. Med Biol 65: 153–157PubMedGoogle Scholar
  20. 20.
    Mody I, Lambert JDC, Heinemann U (1987) Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal sclices. J Neurophysiol 57: 869–888PubMedGoogle Scholar
  21. 21.
    Monaghan DT, Cotman CW (1985) Distribution of N-methyl-d-aspartate-sensitive L-(3H)glutamate binding sites in rat brain. J Neurosci 5: 2909–2919PubMedGoogle Scholar
  22. 22.
    Naas E, Zilles K, Gnahn H, Betz H, Becker C-M, Schröder H (1991) Glycine receptor immunoreactivity in rat and human cerebral cortex. Brain Res (Netherlands) 561(1): 139–146Google Scholar
  23. 23.
    Natale JE, Schott RJ, D'Alecy (1988) Ketamine reduces neurological deficit following 10 minutes of cardiac arrest and resuscitation in canines. In: Domino EF, Kamenka J (eds) Sigma and phencyclidine-like compounds as molecular probes in biology. Ann Arbor: Domino and PP Books, pp 717–726Google Scholar
  24. 24.
    Ohya Y, Ochi N, Mizutani N, Hayakawa C, Watanabe K (1991) Nonketotic hyperglycinemia: treatment with NMDA antagonist and consideration of neuropathogenesis. Pediatr Neurol 7: 65–68PubMedGoogle Scholar
  25. 25.
    Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA (1991) NMDA neurotoxicity: mechanism and prevention. Science 254: 1515–1518PubMedGoogle Scholar
  26. 26.
    Rall TW (1990) Hypnotics and sedatives; ethanol. In: Goodman Gilman A, et al (eds) The pharmacological basis of therapeutics. Pergamon Press, New York (1990) pp 345–382Google Scholar
  27. 27.
    Reich DL, Silvay G (1989) Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 36: 186–197PubMedGoogle Scholar
  28. 28.
    Rothman SW, Olney JW (1987) Excitotoxicity and the NMDA receptor. Trends Neurosci 10: 299–302Google Scholar
  29. 29.
    Schmitt B, Steinmann B, Gitzelmann R, Thun-Hohenstein L, Dumermuth G (1992) Dextromorphan, a N-methyl-d-apartate (NMDA) antagonist, in the treatment of nonketotic hyperglycinemia. 30th Ann. Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM); September 8th–11th, Leuven; Abstracts of Free Communications O 5Google Scholar
  30. 30.
    Slater IH (1971) Strychnine, picrotoxin, pentylenetetrazol, and miscellaneous drugs. In: Drill's Pharmacology in medicine. McGraw-Hill, New York, pp 517–532Google Scholar
  31. 31.
    Süverkrüp R (1985) Segmentally continuous input functions in linear multicompartment systems. J Pharm Sci 74: 136–141PubMedGoogle Scholar
  32. 32.
    Tada K (1987) nonketotic hyperglycinemia. Clinical and metabolic aspects. Recent Adv. Inborn Errors of Metabolism. Proc. 4th Int. Congr., Sendai 1987. Enzyme 38: 27–35Google Scholar
  33. 33.
    Wieber J, Gugler R, Hengstmann JH, Dengler HJ (1975) Pharmacokinetics of ketamine in man. Anaethesist 24: 260–263Google Scholar
  34. 34.
    Wijburg FA, de Groot CJ, Schutgens RBH, Barth PG, Tada K (1988) Clinical effects of serine medication in nonketotic hyperglycinemia due to deficiency of P-protein of the glycin cleavage complex. J Inherited Metab Dis 11 [Suppl 2]: 218–220Google Scholar
  35. 35.
    Wolff JA, Kulovich S, Yu AL, Qiao C-N, Nyhan WL (1986) The effectiveness of benzoate in the management of seizures in nonketotic hyperglycinemia. Am J Dis Child 140: 596–602PubMedGoogle Scholar
  36. 36.
    Young AB, Zukin SR, Snyder SH (1974) Interaction of benzodiazepines with central nervous glycine receptors: Possilble mechanism of action. Proc Natl Acad Sci USA 71: 2246–2250PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Tegtmeyer-Metzdorf
    • 1
  • B. Roth
    • 1
  • M. Günther
    • 1
  • M. Theisohn
    • 2
  • U. Heinemann
    • 3
  • H. A. Adams
    • 4
  • G. Sticht
    • 5
  1. 1.Klinik und Poliklinik für KinderheilkundeUniversität KölnGermany
  2. 2.Institut für PharmacologieUniversität KölnGermany
  3. 3.Institut für NeurophysiologieUniversität KölnGermany
  4. 4.Abteilung für AnacsthesiologieMarienkrankenhausTrierGermany
  5. 5.Institut für GerichtsmedizinUniversität KölnGermany

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