The effects of agomelatine and imipramine on liver cytochrome P450 during chronic mild stress (CMS) in the rat.
Agomelatine
Chronic mild stress (CMS)
Cytochrome P450 activity
Cytochrome P450 expression
Imipramine
Liver
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
23
04
2020
accepted:
27
07
2020
revised:
10
07
2020
pubmed:
5
8
2020
medline:
3
7
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
The 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. Male 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. Agomelatine 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. We 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.
Sections du résumé
BACKGROUND
BACKGROUND
The 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.
METHODS
METHODS
Male 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.
RESULTS
RESULTS
Agomelatine 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.
CONCLUSION
CONCLUSIONS
We 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.
Identifiants
pubmed: 32748256
doi: 10.1007/s43440-020-00151-w
pii: 10.1007/s43440-020-00151-w
pmc: PMC7550324
doi:
Substances chimiques
Acetamides
0
Antidepressive Agents, Tricyclic
0
agomelatine
137R1N49AD
Cytochrome P-450 Enzyme System
9035-51-2
Imipramine
OGG85SX4E4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1271-1287Références
Expert Opin Pharmacother. 2017 Sep;18(13):1373-1379
pubmed: 28730851
Biochem Pharmacol. 2013 Sep 15;86(6):800-7
pubmed: 23924605
Neuropsychobiology. 2005;52(2):90-110
pubmed: 16037678
Hum Psychopharmacol. 2013 Mar;28(2):151-9
pubmed: 23532747
Biochem Pharmacol. 1995 Mar 1;49(5):591-602
pubmed: 7887973
Drug Metab Dispos. 2018 Jun;46(6):786-793
pubmed: 29555828
Anal Bioanal Chem. 2008 Nov;392(6):1085-92
pubmed: 18704375
Br J Pharmacol. 2009 Jun;157(3):342-61
pubmed: 19371342
Pharmacol Rep. 2019 Dec;71(6):1210-1212
pubmed: 31671379
Brain Res. 2012 Jul 23;1466:91-8
pubmed: 22647752
Expert Opin Drug Metab Toxicol. 2013 Oct;9(10):1317-34
pubmed: 23834396
Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):631-45
pubmed: 19442036
J Pharm Pharmacol. 2002 Nov;54(11):1545-52
pubmed: 12495558
Biochem Pharmacol. 2016 Jun 1;109:70-82
pubmed: 27021842
Drug Metab Dispos. 2019 Feb;47(2):80-85
pubmed: 30518657
Pharmacol Rep. 2008 Nov-Dec;60(6):957-65
pubmed: 19211989
Eur Neuropsychopharmacol. 2006 Dec;16(8):580-7
pubmed: 16503401
Psychopharmacology (Berl). 1997 Dec;134(4):319-29
pubmed: 9452163
Expert Opin Drug Metab Toxicol. 2005 Aug;1(2):203-17
pubmed: 16922637
Neuropsychopharmacology. 2009 Oct;34(11):2390-403
pubmed: 19571795
Biochem Biophys Res Commun. 1998 Aug 28;249(3):838-43
pubmed: 9731223
J Pharmacol Exp Ther. 1996 Nov;279(2):724-31
pubmed: 8930177
Pharmacol Rep. 2013;65(5):1247-55
pubmed: 24399720
J Mol Psychiatry. 2015 Apr 21;3(1):4
pubmed: 25932327
CNS Spectr. 2014 Jun;19(3):207-12
pubmed: 24901504
Curr Protoc Pharmacol. 2012 Jun;Chapter 5:Unit 5.9.
pubmed: 22684722
J Biol Rhythms. 1998 Feb;13(1):39-51
pubmed: 9486842
World J Biol Psychiatry. 2010 Mar;11(2):148-53
pubmed: 20109111
Xenobiotica. 2007 Dec;37(12):1355-66
pubmed: 17922362
Pharmacol Res. 2016 Jan;103:1-12
pubmed: 26535964
Behav Pharmacol. 2006 Feb;17(1):9-18
pubmed: 16377959
Pharmacol Res. 2000 Mar;41(3):341-6
pubmed: 10675287
BMC Neurosci. 2010 Jun 03;11:68
pubmed: 20525261
Clin Pharmacol Ther. 1991 Jun;49(6):609-17
pubmed: 2060250
Biochem Pharmacol. 2013 Dec 1;86(11):1614-20
pubmed: 24051135
CNS Neurol Disord Drug Targets. 2007 Oct;6(5):311-20
pubmed: 18045159
Neuropsychiatr Dis Treat. 2009;5:563-76
pubmed: 19966905
Eur J Pharmacol. 2010 Jan 25;626(2-3):171-8
pubmed: 19818757
Physiol Rev. 2009 Apr;89(2):535-606
pubmed: 19342614
J Neuropsychiatry Clin Neurosci. 2012 Summer;24(3):290-308
pubmed: 23037643
Neuropsychopharmacology. 2013 Jan;38(2):275-84
pubmed: 22871919
J Pharmacol Exp Ther. 2003 Sep;306(3):954-64
pubmed: 12750432
Eur Neuropsychopharmacol. 2016 Feb;26(2):378-389
pubmed: 26708320
J Pharmacol Exp Ther. 2007 Apr;321(1):237-48
pubmed: 17237257
Biochem Pharmacol. 2008 Apr 1;75(7):1538-49
pubmed: 18279840
BMC Neurosci. 2013 Jul 29;14:75
pubmed: 23895555
Ann Pharmacother. 2008 Dec;42(12):1822-31
pubmed: 19033480
Mol Pharmacol. 1993 May;43(5):827-32
pubmed: 8502233
Br J Pharmacol. 2014 Aug;171(15):3604-19
pubmed: 24724693
CNS Neurosci Ther. 2010 Aug;16(4):195-207
pubmed: 20236141
Curr Drug Metab. 2014;15(7):694-702
pubmed: 25255870
Drug Metab Dispos. 2017 Dec;45(12):1336-1344
pubmed: 28935656
J Endocrinol Invest. 2014 Nov;37(11):1109-16
pubmed: 25319470
Biochem Pharmacol. 2016 Jul 15;112:82-9
pubmed: 27137992
J Interferon Cytokine Res. 1999 Jun;19(6):601-7
pubmed: 10433360
Eur J Pharmacol. 2003 Feb 28;463(1-3):235-72
pubmed: 12600714
Biochem Pharmacol. 1993 Jan 26;45(2):415-9
pubmed: 8435092
J Psychopharmacol. 2019 Apr;33(4):522-531
pubmed: 30789308
Curr Drug Metab. 2011 Feb;12(2):124-38
pubmed: 21401511
J Clin Psychopharmacol. 1997 Apr;17 Suppl 1:2S-18S
pubmed: 9090573
Psychopharmacology (Berl). 2012 Jun;221(3):493-509
pubmed: 22160164
Biochem Pharmacol. 2018 Oct;156:398-405
pubmed: 30195732
Drug Metab Rev. 2005;37(2):379-404
pubmed: 15931769
Biochem Pharmacol. 2016 Jan 1;99:113-22
pubmed: 26581122
Neurobiol Stress. 2016 Aug 24;6:78-93
pubmed: 28229111
Neuropsychopharmacology. 2003 Apr;28(4):694-703
pubmed: 12655314
Eur J Pharmacol. 1998 Jan 19;342(1):29-37
pubmed: 9544789
Eur Neuropsychopharmacol. 2006 Apr;16(3):178-86
pubmed: 16246530