Relationship between Structure and Metabolism of Tricyclic Drugs: Stable Epdxide-Diol Pathway

  • A. Frigerio
  • C. Pantarotto


Aromatic and olefinic compounds can be metabolized by mammalian microsomal monooxygenases to arene oxides and epoxides respectively. These oxygenated species represent electrophilic intermediates in the formation of phenols and dihydrodiols, which are considered the real detoxification products of these substances (1, 4).


Styrene Oxide Microsomal Preparation Urine Extract Revertant Coloni Tricyclic Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    J.W. Daly, D.M. Jerina and B. Witkop, Experientia, 1972, 28, 1129.PubMedCrossRefGoogle Scholar
  2. 2).
    P.L. Grover, A. Hewer and P. Sims, Biochem. Pharmacol., 1972, 21, 2713.Google Scholar
  3. 3).
    G.R. Keysell, J. Booth, P. Sims, P.L. Grover and A. Hewer, Biochem. J., 1972, 129, 41 P.Google Scholar
  4. 4).
    D.J. Jollow, J.R. Mitchell, N. Zampaglione and J.R. Gillette, Pharmacology, 1974, 11, 151.PubMedCrossRefGoogle Scholar
  5. 5).
    D.M. Jerina and J.W. Daly, Science, 1974, 185, 573.PubMedCrossRefGoogle Scholar
  6. 6).
    J.R. Gillette, Biochem. Pharmacol., 1974, 23, 2785.PubMedCrossRefGoogle Scholar
  7. 7).
    M.J. Cookson, P. Sims and P.L. Grover, Nature New Biol., 1971, 234, 186.PubMedGoogle Scholar
  8. 8).
    T. Kuroki, E. Huberman, H. Marquardt, J.K. Selkirk, C. Heidelberger, P.L. Grover and P. Sims, Chem. Biol. Interactions, 1972, 4, 389.CrossRefGoogle Scholar
  9. 9).
    P.L. Grover, A. Hewer and P. Sims, FEBS Lett., 1971, 18, 76.PubMedCrossRefGoogle Scholar
  10. 10).
    P. Sims, Biochem. Pharmacol., 1970, 19, 795.PubMedCrossRefGoogle Scholar
  11. 11).
    P.L. Grover, A. Hewer and P. Sims, Biochem. Pharmacol., 1974, 23, 323.PubMedCrossRefGoogle Scholar
  12. 12).
    P.L. Grover, Biochem. Pharmacol., 1974, 23, 333.PubMedCrossRefGoogle Scholar
  13. 13).
    G.J. Kasperek, T.C. Bruice, H. Yagi, N. Kaubisch and D.M. Jerina, J. Am. Chem. Soc., 1972, 94, 7876.CrossRefGoogle Scholar
  14. 14).
    T. Chang, A. Savory and A.J. Glazko, Biochem. Biophys. Res. Commun., 1970, 38, 444.CrossRefGoogle Scholar
  15. 15).
    W.G. Stillwell, M. Stafford and M.G. Horning, Res. Commun. Chem. Pathol. Pharmacol., 1973, 6, 579.Google Scholar
  16. 16).
    M. Stafford, G. Kellermann, R.N. Stillwell and M.G. Horning, Res. Commun. Chem. Pathol. Pharmacol., 1974, 8, 593.Google Scholar
  17. 17).
    A. Frigerio, R. Fanelli, P. Biandrate, G. Passerini, P.L. Morselli and S. Garattini, J. Pharm. Sci., 1972, 61, 1144.PubMedCrossRefGoogle Scholar
  18. 18).
    A. Frigerio, N. Sassi, G. Belvedere, C. Pantarotto and S. Garattini, J. Pharm. Sci., 1974, 63, 1536.PubMedCrossRefGoogle Scholar
  19. 19).
    G. Belvedere, V. Rovei, C. Pantarotto and A. Frigerio, Xenobiotica, 1975, 5, 765.CrossRefGoogle Scholar
  20. 20).
    G. Belvedere, C. Pantarotto, V. Rovei and A. Frigerio, J. Pharm. Sci., 1976, 65, 815.PubMedCrossRefGoogle Scholar
  21. 21).
    V. Rovei, G. Belvedere, C. Pantarotto and A. Frigerio, J. Pharm. Sci., 1976, 65, 810.PubMedCrossRefGoogle Scholar
  22. 22).
    A. Frigerio, J. Lanzoni, C. Pantarotto, E. Rossi, V. Rovei and M. Zanol, Xenobiotica, 1976, in press.Google Scholar
  23. 23).
    C. Pantarotto, L. Cappellini, A. De Pascale and A. Frigerio, Xenobiotica, 1976, in press.Google Scholar
  24. 24).
    C. Pantarotto, P. Negrini, L. Cappellini and A. Frigerio, J. Chromatogr., 1976, in press.Google Scholar
  25. 25).
    C.J.W. Brooks and I. Maclean, J. Chromatogr. Sci., 1971, 9, 18.Google Scholar
  26. 26).
    K.M. Baker and A. Frigerio, J. Chem. Soc. (Perkin Trans. II), 1973, 648.Google Scholar
  27. 27).
    J. Pachecka, M. Salmona, L. Cantoni, E. Mussini, C. Pantarotto, A. Frigerio and G. Belvedere, Xenobiotica, 1976, in press.Google Scholar
  28. 28).
    A. Frigerio, K.M. Baker and G. Belvedere, Anal. Chem., 1973, 45, 1846.PubMedCrossRefGoogle Scholar
  29. 29).
    J.W. Faigle, S. Brechbilhler, K.F. Feldmann and W.J. Richter, in “Epileptic Seizures Behaviour Pain”, by W. Birkmayer, Ed., Hans Huber Publishers, Wien, 1976, p. 127.Google Scholar
  30. 30).
    H.B. Hucker, A.J. Balletto, S.C. Stauffer, A.G. Zacchei and B.H. Arison, Drug Metab. Dispos., 1974, 2, 406.PubMedGoogle Scholar
  31. 31).
    C.C. Porter, B.H. Arison, V.F. Gruber, D.C. Titus and W.J.A. Vandenheuvel, Drug Metab. Dispos., 1975, 3, 189.PubMedGoogle Scholar
  32. 32).
    H.B. Hucker, A.J. Balletto, J. Demetriades, B.H. Arison and A.G. Zacchei, Drug Metab. Dispos., 1975, 3, 80.PubMedGoogle Scholar
  33. 33).
    G. Belvedere, V. Rovei, C. Pantarotto and A. Frigerio, Biomed. Mass Spectrom., 1974, 1, 329.PubMedCrossRefGoogle Scholar
  34. 34).
    A. Frigerio and P.L. Morselli, in “Advances in Neurology”, Vol. 11, J.K. Penry and D.D. Daly, Eds., Raven Press, New York, 1975, p. 295.Google Scholar
  35. 35).
    A. Bonaccorsi, R. Franco and P.L. Morselli, unpublished results.Google Scholar
  36. 36).
    L. Morasca, unpublished results.Google Scholar
  37. 37).
    F. Spreafico, unpublished results.Google Scholar
  38. 38).
    H.R. Glatt, F. Oesch, A. Frigerio and S. Garattini, Int. J. Cancer, 1975, 16, 787.PubMedCrossRefGoogle Scholar
  39. 39).
    G. Belvedere, C. Pantarotto and A. Frigerio, Biomed. Mass Spectrom., 1975, 2, 115.CrossRefGoogle Scholar
  40. 40).
    J. Pachecka, M. Salmona, G. Belvedere, L. Cantoni, E. Mussini and S. Garattini, Experientia, 1976, in press.Google Scholar
  41. 41).
    F. Oesch, P. Bentley and H.R. Glatt, in “Active Intermediates: Formation, Toxicity and Inactivation”, J.R. Gillette, D. Jollow, J.J. Kocsis, H. Remmer, R. Snyder, H. Vainio and A. Hanninen, Eds., Plenum Publishing Company, New York, 1976, in press.Google Scholar
  42. 42).
    H. Kappus and H. Remmer, Biochem. Pharmacol., 1975, 24, 1079.PubMedCrossRefGoogle Scholar
  43. 43).
    A. Frigerio and C. Pantarotto, J. Pharm. Pharmacol., 1976, 28, 665.PubMedCrossRefGoogle Scholar
  44. 44).
    W.E. Crill, Ann. Intern. Med., 1973, 79, 844.PubMedGoogle Scholar
  45. 45).
    J.S. Wold and L.J. Fischer, J. Pharmacol. Exp. Ther., 1972, 183, 188.PubMedGoogle Scholar
  46. 46).
    F. Oesch, H. Thoenen and H. Fahrlaender, Biochem. Pharmacol., 1974, 23, 1307.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • A. Frigerio
    • 1
  • C. Pantarotto
    • 1
  1. 1.Istituto Ricerche Farmacologiche “Mario Negri”MilanItaly

Personalised recommendations