Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain.
7-dehydrocholesterol
aripiprazole
brain regions
cholesterol
desmosterol
mouse model
polypharmacy
side effects
sterol homeostasis
trazodone
Journal
Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
07
05
2022
revised:
29
06
2022
accepted:
30
06
2022
pubmed:
16
7
2022
medline:
31
8
2022
entrez:
15
7
2022
Statut:
ppublish
Résumé
Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions between two commonly prescribed psychotropic medications with sterol inhibiting side effects, trazodone (TRZ), an antidepressant, and aripiprazole (ARI), an antipsychotic. In vitro cell culture experiments revealed that both medications alone disrupted neuronal and astroglial sterol biosynthesis in dose-dependent manners. Furthermore, when ARI and TRZ were combined, exposure resulted in an additive 7-dehydrocholesterol (7-DHC) increase, as well as desmosterol (DES) and cholesterol decreases in both cell types. In adult mice, at baseline, we found that the three investigated sterols showed significant differences in distribution across the eight assessed brain regions. Furthermore, experimental mice treated with ARI or TRZ, or a combination of both medications for 8 days, showed strong sterol disruption across all brain regions. We show ARI or TRZ alone elevated 7-DHC and decreased DES levels in all brain regions, but with regional differences. However, the combined utilization of these two medications for 8 days did not lead to additive changes in sterol disturbances. Based on the complex roles of 7-DHC derived oxysterols, we conclude that individual and potentially simultaneous use of medications with sterol biosynthesis-inhibiting properties might have undesired side effects on the adult brain, with as yet unknown long-term consequences on mental or physical health.
Identifiants
pubmed: 35839864
pii: S0022-2275(22)00082-7
doi: 10.1016/j.jlr.2022.100249
pmc: PMC9386463
pii:
doi:
Substances chimiques
Antidepressive Agents
0
Antipsychotic Agents
0
Sterols
0
Aripiprazole
82VFR53I78
Oxidoreductases Acting on CH-CH Group Donors
EC 1.3.-
Trazodone
YBK48BXK30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100249Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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