ArticlePharmacological reports : PR2020
The effects of agomelatine and imipramine on liver cytochrome P450 during chronic mild stress (CMS) in the rat.
Article in Pharmacological reports : PR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- The neuroendocrine regulation of hepatic cytochrome P450 by N-methyl-D-aspartate receptors in the paraventricular and arcuate nuclei of the hypothalamus.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Importance of additional behavioral observation in psychopharmacology: a case study on agomelatine's effects on feedback sensitivity in probabilistic reversal learning in rats.Psychopharmacology · 2025Article
- Development of a Novel In Silico Classification Model to Assess Reactive Metabolite Formation in the Cysteine Trapping Assay and Investigation of Important Substructures.Biomolecules · 2024Article
- CYP1A2 polymorphism may contribute to agomelatine-induced acute liver injury: Case report and review of the literature.Medicine · 2021Review
- Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.Frontiers in pharmacology · 2021Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of our research was to determine the effects of chronic treatment with the atypical antidepressant agomelatine on the expression and activity of liver cytochrome P450 (CYP) in the chronic mild stress (CMS) model of depression, and to compare the results with those obtained for the first-generation antidepressant imipramine.
methodsMale Wistar rats were subjected to CMS for 7 weeks. Imipramine (10 mg/kg ip/day) or agomelatine (40 mg/kg ip/day) was administered to nonstressed or stressed animals for 5 weeks (weeks 3-7 of CMS). The levels of cytochrome P450 mRNA, protein and activity were measured in the liver.
resultsAgomelatine and imipramine produced different broad-spectrum effects on cytochrome P450. Like imipramine, agomelatine increased the expression/activity of CYP2B and CYP2C6, and decreased the CYP2D activity. Unlike imipramine, agomelatine raised the expression/activity of CYP1A, CYP2A and reduced that of CYP2C11 and CYP3A. CMS modified the effects of antidepressants at transcriptional/posttranscriptional level; however, the enzyme activity in stressed rats remained similar to that in nonstressed animals. CMS alone decreased the CYP2B1 mRNA level and increased that of CYP2C11.
conclusionWe conclude the following: (1) the effects of agomelatine and imipramine on cytochrome P450 are different and involve both central and peripheral regulatory mechanisms, which implicates the possibility of drug-drug interactions; (2) CMS influences the effects of antidepressants on cytochrome P450 expression, but does not change appreciably their effects on the enzyme activity. This suggests that the rate of antidepressant drug metabolism under CMS is similar to that under normal conditions.
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