Skip to main content
Log in

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative

  • Original Papers
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

Pretreatment with taglutimide significantly decreased the plasma dicoumarol level and shortened the duration of hexobarbital-induced narcosis in rats. Furthermore, taglutimide pretreatment accelerated thein vitro metabolism of dicoumarol, hexobarbital, o-nitrophenyl acetate and procaine, but not of 3,4-benzpyrene, as assayed in the 10,000xg supernatant fraction of rat liver homogenate. No definite increase was observed in liver wet weight, nor in the amount of microsomal and total liver protein in comparison with the control values. No marked differences were found between the effects of short-(4-day) and long-term (17-day) pretreatment on any of the studied parameters. The changes in drug metabolism and liver protein observed after taglutimide pretreatment differed from those observed after pretreatment with either phenobarbital or 3,4-benzpyrene. Taglutimide, like other inducing agents, is lipophilic, but differs from them in not being a substrate of monooxygenases.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Koehler F. and Koch H. (1974): Teratologische Untersuchungen der Thalidomid-aehnlichen Verbindungen K-2004 und K-2604 an Maus und Ratte. Arzneim.-Forsch.,24, 1616–1619.

    CAS  Google Scholar 

  2. Argyropoulos G., Lanner G. and Pasquali E. (1976): Klinische und elektroenzephalographische Studien mit einem neuen Hypnosedativum K-2004. Wien. Med. Wschr.,126, 75–77.

    CAS  PubMed  Google Scholar 

  3. Schuetzenberger W.G., Kolassa N., Wiener H., Kraupp O., and Tuisl E. (1979): Pharmacological properties of biglumide, a new sedative hypnotic drug. Arzneim.-Forsch.,29, 1146–1150.

    CAS  Google Scholar 

  4. Remmer H. (1962): in “Symp. Redoxfunktionen Cytoplasmatischer Strukturen”, Gemeinsame Tagung Dtsch. Ges. Physiol. Chem. und Oesterr. Biochem. Ges. in Wien, p. 75.

  5. Kato R., Chiesara E. and Vassanelli P. (1964): Further studies on the inhibition and stimulation of microsomal drug-metabolizing enzymes of rat liver by various compounds. Biochem. Pharmac.,13, 69–83.

    Article  CAS  Google Scholar 

  6. Conney A.H. (1967): Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev.19, 317–366.

    CAS  PubMed  Google Scholar 

  7. Hunter J. and Chasseaud L.F. (1976): Clinical aspects of microsomal enzyme induction. In “Progress in Drug Metabolism” (J.W. Bridges and L.F. Chasseaud, eds.), Vol. 1, p. 129–191. John Wiley & Sons, London.

    Google Scholar 

  8. Zaroslinski J., Browne R. and Possley L. (1972): Effect of subacute administration of methaqualone, phenobarbital and glutethimide on plasma levels of bishydroxycoumarin. Arch. int. Pharmacodyn.,195, 185–191.

    CAS  PubMed  Google Scholar 

  9. Axelrod J., Cooper J.R. and Brodie B.B. (1949): Estimation of dicumarol, 3,3-methylenebis(4-hydroxycoumarin) in biological fluids. Proc. Soc. Exp. Biol. Med.,70, 693–695.

    CAS  PubMed  Google Scholar 

  10. Conney A.H., Davison C., Gastel R. and Burns J.J. (1960): Adaptive increases in drug-metabolizing enzymes induced by phenobarbital and other drugs. J. Pharmacol. Exp. Ther.,130, 1–8.

    CAS  PubMed  Google Scholar 

  11. Mazel P. (1971): Experiments illustrating drug metabolism in vitro. In “Fundamentals of Drug Metabolism and Drug Disposition” (B.N. La Du, H.G. Mandel and E.L. Way, eds.), p. 546–582, Williams & Wilkins Co., Baltimore.

    Google Scholar 

  12. Layne E. (1957). Spectrophotometric and turbidimetric methods for measuring proteins. In “Methods in Enzymology” (S.P. Colowick and N.O. Kaplan, eds.), Vol. 3, p. 447–454, Academic Press, New York.

    Google Scholar 

  13. Cooper J.R. and Brodie B.B. (1955): The enzymatic metabolism of hexobarbital (evipal). J. Pharmacol. Exp. Ther.,114, 409–417.

    CAS  PubMed  Google Scholar 

  14. Remmer H. and Merker H.J. (1963): Drug-induced changes in the liver endoplasmic reticulum: Association with drug-metabolizing enzymes. Science,142, 1657–1658.

    Article  CAS  PubMed  Google Scholar 

  15. Conney A.H., Miller E.C. and Miller J.A. (1957): Substrate-induced synthesis and other properties of benzpyrene hydroxylase in rat liver. J. Biol. Chem.,228, 753–766.

    CAS  PubMed  Google Scholar 

  16. Krisch K. (1966): Reaction of a microsomal esterase from hog-liver with diethyl p-nitrophenyl phosphate. Biochim. Biophys. Acta.,122, 265–280.

    CAS  PubMed  Google Scholar 

  17. Koch-Weser J. and Sellers E.M. (1971): Drug interactions with coumarin anticoagulants. I. New. Engl. J. Med.,285, 487–498.

    Article  CAS  Google Scholar 

  18. Barker W.M., Hermodson M.A. and Link K.P. (1970): The metabolism of 4-C14-warfarin sodium by the rat. J. Pharmacol. Exp. Ther.,171, 307–313.

    CAS  PubMed  Google Scholar 

  19. Kaighen M. and Williams R.T. (1961): Metabolism of coumarin-3-C14. J. med. pharm. Chem.,3, 25–43.

    Article  CAS  Google Scholar 

  20. Pischek G., Kaiser E. and Koch H. (1974): Thalidomid-Analoga, 5. Mitt.: Untersuchungen zum Metabolismus der Thalidomid-aehnlichen Verbindung K-2004. Monatsh. Chem.,105, 74–79.

    Article  CAS  Google Scholar 

  21. Pischek G. and Koch H. (1976): Thalidomid-Analoga, 7. Mitt.: Metabolisierung und Elimination der Thalidomidaehnlichen Verbindungen K-2004 bei der Ratte. Arch. Pharm.,309, 62–69.

    Article  CAS  Google Scholar 

  22. Aggeler P.M. and O’Reilly R.A. (1969): Effect of heptabarbital on the response to bishydroxycoumarin in man. J. Lab. Clin. Med.,74, 229–238.

    CAS  PubMed  Google Scholar 

  23. Conney A.H. (1971): Environmental factors influencing drug metabolism. In “Fundamentals of Drug Metabolism and Drug Disposition” (B.N. La Du, H.G. Mandel and E.L. Way, eds.), p. 253–278, Williams & Wilkins Co., Baltimore.

    Google Scholar 

  24. Breckenridge A., Orme M.L’E., Davies L., Thorgeirsson S.S. and Davies D.S. (1973): Dose-dependent enzyme induction. Clin. Pharmacol. Ther.,14, 514–520.

    CAS  PubMed  Google Scholar 

  25. Moroi K. and Satoh T. (1975): Modification of procaine metabolism in rat liver after administration of phenobarbital or ethyl p-nitrophenyl phenylphosphonothioate. Biochem. Pharmac.,24, 1436–1438.

    Article  CAS  Google Scholar 

  26. Gram T.E. and Gillette J.R. (1971): Biotransformation of drugs. In “Fundamentals of Biochemical Pharmacology” (Z.M. Bacq, ed.), p. 571–609, Pergamon Press, Oxford.

    Google Scholar 

  27. Goldschmidt S. and Wehr R. (1957): Ueber Barbiturate, III. Mitteilung. Der Metabolismus von Veronal. Hoppe-Seyler’s Z. Physiol. Chem.,308, 9–19.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wiener, H., Krivanek, P., Tuisl, E. et al. Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative. European Journal of Drug Metabolism and Pharmacokinetics 5, 93–97 (1980). https://doi.org/10.1007/BF03189451

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03189451

Key-words

Navigation