Role of CYP2E1 in deramciclane metabolism

Katalin Monostory, Krisztina Köhalmy, Eszter Hazai, László Vereczkey, László Kóbori

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The aim of our study was to identify the form(s) of cytochrome P450 responsible for the metabolism of deramciclane, a new anxiolytic drug candidate. The main routes of biotransformation in hepatic microsomes were side chain modification (N-demethylation or total side chain cleavage) and hydroxylation at several points of the molecule. Although several cytochrome P450 forms were involved in the metabolism, the role of CYP2E1 should be emphasized, since it catalyzed almost all steps. Production of deramciclane metabolites was significantly inhibited by diethyldithiocarbamate and was elevated in liver microsomes of isoniazid-treated rats. Furthermore, cDNA-expressed rat CYP2E1 generated the metabolites formed by side chain modification and hydroxylation. Neither deramciclane nor its primary metabolite, N-desmethyl deramciclane were able to influence directly the activity of CYP2E1. However, during the biotransformation, one or more metabolites must have been formed which were potent inhibitors of CYP2E1.

Original languageEnglish
Pages (from-to)1717-1722
Number of pages6
JournalDrug Metabolism and Disposition
Volume33
Issue number11
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Cytochrome P-450 CYP2E1
Metabolites
Metabolism
Hydroxylation
Biotransformation
Cytochrome P-450 Enzyme System
Rats
Ditiocarb
Anti-Anxiety Agents
Isoniazid
Liver Microsomes
Microsomes
Liver
Complementary DNA
Molecules
deramciclane
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Role of CYP2E1 in deramciclane metabolism. / Monostory, Katalin; Köhalmy, Krisztina; Hazai, Eszter; Vereczkey, László; Kóbori, László.

In: Drug Metabolism and Disposition, Vol. 33, No. 11, 11.2005, p. 1717-1722.

Research output: Contribution to journalArticle

Monostory, Katalin ; Köhalmy, Krisztina ; Hazai, Eszter ; Vereczkey, László ; Kóbori, László. / Role of CYP2E1 in deramciclane metabolism. In: Drug Metabolism and Disposition. 2005 ; Vol. 33, No. 11. pp. 1717-1722.
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