Altmetric

NMR-based metabonomic analysis of normal rat urine and faeces in response to (+/-)-venlafaxine treatment

Title: NMR-based metabonomic analysis of normal rat urine and faeces in response to (+/-)-venlafaxine treatment
Authors: Serrano-Contreras, JI
Garcia-Perez, I
Melendez-Camargo, ME
Zepeda-Vallejo, LG
Item Type: Journal Article
Abstract: (±)-Venlafaxine, a bicyclic antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class, is prescribed for the treatment of depression and anxiety disorders. As is the case with other antidepressants, its precise mechanisms of action are still unknown. Pharmacometabonomic approaches allow for the detection of diverse metabolites, unlike classic methods for analysing drug interaction based on single metabolites and linear pathways. This provides a global view of the state of homeostasis during treatment and an insight into the mechanisms of action of a drug. Accordingly, the final outcome of treatment is characterised by the network of reactome pathways derived from the on-target and off-target effects of the drug. Regarding antidepressants, the drug network may be located in the gut–microbiome–brain–liver–kidney–immune–cardiovascular system axis (GMBLKICA), implying that neurotransmitters participate as signalling molecules in bidirectional communication. If their bioavailability is increased, this communication and the state of homeostasis may be disrupted. With a pharmacometabonomic approach using NMR in combination with different chemometric methods, a determination was made of subtle changes in the metabolic profile (metabotype) of urine and faeces in normal Wistar rats following a single administration of pharmacological doses of (±)-venlafaxine hydrochloride. Based on the drug-response metabotypes observed, (±)-venlafaxine had effects on gut microbial co-metabolites and osmolytes. Hence, it can be hypothesized that bidirectional communication in the multiorgan axis was perturbed by this drug, and very likely by its active metabolite, (±)-desvenlafaxine. This disrupted signalling could be related not only to therapeutic and adverse effects, but also to the lag period in treatment response.
Issue Date: 1-Feb-2016
Date of Acceptance: 19-Jan-2016
URI: http://hdl.handle.net/10044/1/49445
DOI: https://dx.doi.org/10.1016/j.jpba.2016.01.044
ISSN: 0731-7085
Publisher: Elsevier
Start Page: 82
End Page: 92
Journal / Book Title: Journal of Pharmaceutical and Biomedical Analysis
Volume: 123
Copyright Statement: © 2016 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology
Physical Sciences
Life Sciences & Biomedicine
Chemistry, Analytical
Pharmacology & Pharmacy
Chemistry
NMR-based pharmacometabonomics
Gut microbial co-metabolite
(+/-)-Venlafaxine
Xenometabolome
Multiorgan axis
Multivariate data analysis
TOTAL CORRELATION SPECTROSCOPY
GUT MICROBIOTA
BRAIN
IDENTIFICATION
DEPRESSION
SEROTONIN
DISEASE
ACCOUNT
MOUSE
(±)-Venlafaxine
Animals
Antidepressive Agents
Brain
Depression
Desvenlafaxine Succinate
Feces
Female
Magnetic Resonance Imaging
Metabolomics
Neurotransmitter Agents
Norepinephrine
Rats
Rats, Wistar
Serotonin Uptake Inhibitors
Urine
Venlafaxine Hydrochloride
0301 Analytical Chemistry
1115 Pharmacology And Pharmaceutical Sciences
Analytical Chemistry
Publication Status: Published
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx