Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 277, Issue 4, pp 323–332 | Cite as

Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism

  • J. Krieglstein
  • R. Stock
Article

Summary

The isolated perfused rat brain was used for a comparative study of the effects of chloral hydrate and trichloroethanol on cerebral energy metabolism. After a perfusion period of 30 min the brain levels of the following substrates and metabolites were measured spectrophotometrically: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, α-glycero-P, dihydroxyacetone-P, pyruvate, lactate, glutamate, α-ketoglutarate and ammonia. Furthermore, the concentration of chloral hydrate and trichloroethanol in the isolated brain and in the perfusion medium was measured colorimetrically. Little more than 10% of chloral hydrate in the isolated brain and in the perfusion medium were reduced to trichloroethanol. In intact animals there were about 70% of chloral hydrate transformed. Chloral hydrate and trichloroethanol caused an accumulation of P-creatine, no change in the lactate/pyruvate ratio, an increase of the glucose concentration and a decrease of glucose-6-P level in the isolated brain. The rise of brain glucose level was more pronounced after trichloroethanol than after chloral hydrate. The effects of chloral hydrate and trichloroethanol on brain glucose and glucose-6-P levels suggest an inhibition of brain hexokinase activity by these drugs.

Key words

Chloral Hydrate Trichloroethanol Isolated Perfused Rat Brain High-Energy Phosphates Glycolytic Pathway 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andjus, R. K., Suhara, K., Sloviter, H. A.: An isolated perfused rat brain preparation, its spontaneous and stimulated activity. J. appl. Physiol. 22, 1033–1039 (1967).Google Scholar
  2. Bergmeyer, H. U.: Methoden der enzymatischen Analyse, 2. Aufl. Weinheim: Verlag Chemie 1970.Google Scholar
  3. Buchel, L.: Contribution à l'etude du metabolisme de l'hydrate de chloral chez les rongeurs. I. Chez le rat. Arch. Sci. physiol. 18, 115–122 (1964).Google Scholar
  4. Butler, T. C.: The metabolic fate of chloral hydrate. J. Pharmacol. exp. Ther. 92, 49–58 (1948).Google Scholar
  5. Butler, T. C.: Reduction and oxidation of chloral hydrate by isolated tissues in vitro. J. Pharmacol. exp. Ther. 95, 360–362 (1949).Google Scholar
  6. Cooper, J. R., Friedman, P. J.: The enzymic oxidation of chloral hydrate to trichloroacetic acid. Biochem. Pharmacol. 1, 76–82 (1958)Google Scholar
  7. Fleck, W., Krieglstein, J., Urban, W.: Zwei Apparaturen zur Perfusion des isolierten Rattenhirns. Arzneimittel-Forsch. 22, 1225–1230 (1972).Google Scholar
  8. Friedman, P. J., Cooper, J. R.: Determination of chloral hydrate, trichloroacetic acid and trichloroethanol. Analyt. Chem. 30, 1674–1676 (1958).Google Scholar
  9. Friedman, P. J., Cooper, J. R.: The role of alcohol dehydrogenase in the metabolism of chloral hydrate. J. Pharmacol. exp. Ther. 129, 373–376 (1960).Google Scholar
  10. Gatfield, P. D., Lowry, O. H., Schulz, D. W., Passonneau, J. V.: Regional energy reserves in mouse brain and changes with ischaemia and anaesthesia. J. Neurochem. 13, 185–195 (1966).Google Scholar
  11. Granholm, L., Kaasik, A. E., Nilsson, L., Siesjö, B. K.: The lactate/pyruvate ratios of cerebrospinal fluid of rats and cats related to the lactate/pyruvate, the ATP/ADP, and the phosphocreatine/creatine ratios of brain tissues. Acta physiol. scand. 74, 398–409 (1968).Google Scholar
  12. Grüner, J., Krieglstein, J., Rieger, H.: Comparison of the effects of chloral hydrate and trichloroethanol on the EEG of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 333–348 (1973).Google Scholar
  13. Krieglstein, J., Grüner, J., Stock, R.: Effects of chloral hydrate and rrichloroethanol on energy metabolism and EEG of the isolated perfused rat brain. Abstracts of Volunteer Papers, p. 130, Fifth International Congress on Pharmacology, San Francisco, 1972c.Google Scholar
  14. Krieglstein, G., Krieglstein, J., Stock, R.: Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 124–134 (1972a).Google Scholar
  15. Krieglstein, G., Krieglstein, J., Urban, W.: Long survival time of an isolated perfused rat brain. J. Neurochem. 19, 885–886 (1972b).Google Scholar
  16. Lowry, O. H., Passonneau, J. V., Hasselberger, F. X., Schulz, D. W.: Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J. biol. Chem. 239, 18–30 (1964).Google Scholar
  17. MacFadyen, D. A.: Estimation of formaldehyde in biological mixtures. J. biol. Chem. 158, 107–133 (1945).Google Scholar
  18. MacKay, F. J., Cooper, J. R.: A study on the hypnotic activity of chloral hydrate. J. Pharmacol. exp. Ther. 135, 271–274 (1962).Google Scholar
  19. Marshall, E. K., Owens, A. H.: Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol. Bull. Johns Hopk. Hosp. 95, 1–18 (1954).Google Scholar
  20. Schmahl, F. W., Betz, E., Talke, H., Hohorst, H. J.: Energiereiche Phosphate und Metabolite des Energiestoffwechsels in der Großhirnrinde der Katze. Biochem. Z. 342, 518–531 (1965).Google Scholar
  21. Wilson, W. S.: The effects of phenobarbitone, leptazol, dexamphetamine, iproniazid, imipramine, LSD, chlorpromazine, reserpine and hydroxyzine on the in vivo levels of adenine nucleotides and phosphocreatine in the rat brain. Brit. J. Pharmacol. 36, 448–457 (1969).Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • J. Krieglstein
    • 1
  • R. Stock
    • 1
  1. 1.Pharmakologisches Institut der Universität MainzMainzGermany

Personalised recommendations