Skip to main content
Log in

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

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

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).

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.

Institutional subscriptions

Similar content being viewed by others

References

  • von Bahr C, Orrenius S, Sjöqvist F (1971) Interaction of imipramine, desmethylimipramine, nortriptyline and 1-naphthol with microsomal preparations. Chem Biol Interact 3:243–244

    Google Scholar 

  • Beaubien AR, Pakuts AP (1979) Influence dose on first-pass kinetics of 14C-imipramine in the isolated perfused rat liver. Drug Met Disp 7:34–39

    Google Scholar 

  • 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: 433–463

    Google Scholar 

  • Breyer U (1972) Perazine, chlorpromazine and imipramine as inducers of microsomal drug metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 272:277–288

    Google Scholar 

  • 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) 11:255–264

    Google Scholar 

  • 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 317:209–213

    Google Scholar 

  • Dingell JV, Sulser F, Gillette JR (1964) Species differences in the metabolism of imipramine and desmethyl-imipramine (DMI). J Pharmacol Exp Ther 143:14–22

    Google Scholar 

  • Duncan DA (1955) Multiple range and multiple F tests. Biometrics 11:1–42

    Google Scholar 

  • Haugen DA, van der Hoeven TA, Coon MJ (1975) Purified liver microsomal cytochrome P-450. J Biol Chem 250:3567–3570

    Google Scholar 

  • Kakemi K, Sezaki H, Konishi R, Kimura T (1971) Inhibitory mechanism of imipramine on barbiturate metabolism in rat liver. Chem Pharm Bull 19:1395–1401

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Müller-Enoch D, Thomas H, Ockenfels H (1979) Eine fluorimetrische Bestimmungsmethode für mikrosomale Monooxygenase-Aktivität der Rattenleber mit Scoparon als Substrat. Z Naturforsch 34c:481–482

    Google Scholar 

  • Nagy A, Johansson R (1975) Plasma levels of imipramine and desipramine in man after different routes of administration. Naunyn-Schmiedeberg's Arch Pharmacol 290:145–160

    Google Scholar 

  • Nakazawa K (1970) Studies on the demethylation, hydroxylation and N-oxidation of imipramine in rat liver. Biochem Pharmacol 19:1363–1369

    Google Scholar 

  • Nash T (1953) The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J 55:416–421

    Google Scholar 

  • Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378

    Google Scholar 

  • Shand DG, Oates JA (1971) Metabolism of propranolol by rat liver microsomes and its inhibition by phenothiazine and tricyclic antidepressant drugs. Biochem Pharmacol 20:1720–1723

    Google Scholar 

  • 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.): R11

    Google Scholar 

  • Ziegler DM, Mitchell CH (1972) Microsomal oxidase. IV. Properties of a mixed function amine oxidase isolated from pig liver microsomes. Arch Biochem Biophys 150:116–125

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daniel, W., Friebertschäuser, J. & Steffen, C. The effect of imipramine and desipramine on mixed function oxidase in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 83–86 (1984). https://doi.org/10.1007/BF00496111

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00496111

Key words

Navigation