PT  - JOURNAL ARTICLE
AU  - Katalin Monostory
AU  - Krisztina Köhalmy
AU  - Eszter Hazai
AU  - László Vereczkey
AU  - László Kóbori
TI  - ROLE OF CYP2E1 IN DERAMCICLANE METABOLISM
AID  - 10.1124/dmd.105.003772
DP  - 2005 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1717--1722
VI  - 33
IP  - 11
4099  - http://dmd.aspetjournals.org/content/33/11/1717.short
4100  - http://dmd.aspetjournals.org/content/33/11/1717.full
SO  - Drug Metab Dispos2005 Nov 01; 33
AB  - 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 diethyl-dithiocarbamate 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. The American Society for Pharmacology and Experimental Therapeutics