Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 328, Issue 1, pp 83–86 | Cite as

The effect of imipramine and desipramine on mixed function oxidase in rats

  • W. Daniel
  • J. Friebertschäuser
  • C. Steffen


The effects of imipramine and desipramine on hepatic mixed function oxidase were measured in male Wistar rats. Both antidepressants increased hepatic cytochrome P-450 when given b.i.d. for 7 or 14 days. In vitro demethylation of imipramine was rather depressed than increased. 14CO2 exhalation from [N-methyl-14C] benzphetamine was increased by pretreatment with the antidepressants as well as with phenobarbital, but imipramine had no influence on the exhalation of the label from [6-methoxy-14C]-or [7-methoxy-14C]-scoparone.

No difference was observed between treatment with imipramine or desipramine. It is concluded that changes of the demethylation rate of imipramine are not responsible for its delayed elimination observed after chronic treatment (Daniel et al. 1981).

Key words

Imipramine Desipramine Cytochrome P-450 Drug metabolism 14CO2 breath test 


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  1. von Bahr C, Orrenius S, Sjöqvist F (1971) Interaction of imipramine, desmethylimipramine, nortriptyline and 1-naphthol with microsomal preparations. Chem Biol Interact 3:243–244Google Scholar
  2. Beaubien AR, Pakuts AP (1979) Influence dose on first-pass kinetics of 14C-imipramine in the isolated perfused rat liver. Drug Met Disp 7:34–39Google Scholar
  3. Bickel MH, Weder HJ (1968) The total fate of a drug: kinetics of distribution, excretion, and formation of 14 metabolites in rats treated with imipramine. Arch Int Pharmacodyn Ther 173: 433–463Google Scholar
  4. Breyer U (1972) Perazine, chlorpromazine and imipramine as inducers of microsomal drug metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 272:277–288Google Scholar
  5. Christiansen J, Gram LF, Kofod B, Rafaelsen OJ (1967) Imipramine metabolism in man. A study of urinary metabolites after administration of radioactive imipramine. Psychopharm (Berlin) 11:255–264Google Scholar
  6. Daniel W, Adamus A, Melzacka M, Szymura J, Vetulani J (1981) Cerebral pharmacokinetics of imipramine in rats after single and multiple dosages. Naunyn-Schmiedeberg's Arch Pharmacol 317:209–213Google Scholar
  7. Dingell JV, Sulser F, Gillette JR (1964) Species differences in the metabolism of imipramine and desmethyl-imipramine (DMI). J Pharmacol Exp Ther 143:14–22Google Scholar
  8. Duncan DA (1955) Multiple range and multiple F tests. Biometrics 11:1–42Google Scholar
  9. Haugen DA, van der Hoeven TA, Coon MJ (1975) Purified liver microsomal cytochrome P-450. J Biol Chem 250:3567–3570Google Scholar
  10. Kakemi K, Sezaki H, Konishi R, Kimura T (1971) Inhibitory mechanism of imipramine on barbiturate metabolism in rat liver. Chem Pharm Bull 19:1395–1401Google Scholar
  11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  12. Müller-Enoch D, Thomas H, Ockenfels H (1979) Eine fluorimetrische Bestimmungsmethode für mikrosomale Monooxygenase-Aktivität der Rattenleber mit Scoparon als Substrat. Z Naturforsch 34c:481–482Google Scholar
  13. Nagy A, Johansson R (1975) Plasma levels of imipramine and desipramine in man after different routes of administration. Naunyn-Schmiedeberg's Arch Pharmacol 290:145–160Google Scholar
  14. Nakazawa K (1970) Studies on the demethylation, hydroxylation and N-oxidation of imipramine in rat liver. Biochem Pharmacol 19:1363–1369Google Scholar
  15. Nash T (1953) The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 55:416–421Google Scholar
  16. Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378Google Scholar
  17. Shand DG, Oates JA (1971) Metabolism of propranolol by rat liver microsomes and its inhibition by phenothiazine and tricyclic antidepressant drugs. Biochem Pharmacol 20:1720–1723Google Scholar
  18. Steffen C, Wittig M (1984) Effects of phenobarbital and 3-methylcholanthrene on the blood kinetics of methacetin and 14CO2 exhalation in rats. Naunyn-Schmiedeberg's Arch Pharmacol 325 (Suppl.): R11Google Scholar
  19. Ziegler DM, Mitchell CH (1972) Microsomal oxidase. IV. Properties of a mixed function amine oxidase isolated from pig liver microsomes. Arch Biochem Biophys 150:116–125Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • W. Daniel
    • 2
  • J. Friebertschäuser
    • 1
  • C. Steffen
    • 1
  1. 1.Department of PharmacologyPhilipps-UniversityMarburgGermany
  2. 2.Department of Biochemistry, Institute of PharmacologyPolish Academy of SciencesKrakowPoland

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