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Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist

Depression is the most common mental illness, affecting approximately 4.4% of the global population. Despite many available treatments, some patients exhibit treatment-resistant depression. Thus, the need to develop new and alternative treatments cannot be overstated. Adenosine receptor antagonists...

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Autores principales: Smith, Arnold Petrus, Lindeque, Jeremie Zander, van der Walt, Mietha Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000263/
https://www.ncbi.nlm.nih.gov/pubmed/35408500
http://dx.doi.org/10.3390/molecules27072094
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author Smith, Arnold Petrus
Lindeque, Jeremie Zander
van der Walt, Mietha Magdalena
author_facet Smith, Arnold Petrus
Lindeque, Jeremie Zander
van der Walt, Mietha Magdalena
author_sort Smith, Arnold Petrus
collection PubMed
description Depression is the most common mental illness, affecting approximately 4.4% of the global population. Despite many available treatments, some patients exhibit treatment-resistant depression. Thus, the need to develop new and alternative treatments cannot be overstated. Adenosine receptor antagonists have emerged as a promising new class of antidepressants. The current study investigates a novel dual A(1)/A(2A) adenosine receptor antagonist, namely 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (1a), for antidepressant capabilities by determining its metabolic profiles and comparing them to those of two reference compounds (imipramine and KW-6002). The metabolic profiles were obtained by treating male Sprague-Dawley rats with 1a and the reference compounds and subjecting them to the forced swim test. Serum and brain material was consequently collected from the animals following euthanasia, after which the metabolites were extracted and analyzed through untargeted metabolomics using both (1)H-NMR and GC-TOFMS. The current study provides insight into compound 1a’s metabolic profile. The metabolic profile of 1a was similar to those of the reference compounds. They potentially exhibit their antidepressive capabilities via downstream effects on amino acid and lipid metabolism.
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spelling pubmed-90002632022-04-12 Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist Smith, Arnold Petrus Lindeque, Jeremie Zander van der Walt, Mietha Magdalena Molecules Article Depression is the most common mental illness, affecting approximately 4.4% of the global population. Despite many available treatments, some patients exhibit treatment-resistant depression. Thus, the need to develop new and alternative treatments cannot be overstated. Adenosine receptor antagonists have emerged as a promising new class of antidepressants. The current study investigates a novel dual A(1)/A(2A) adenosine receptor antagonist, namely 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (1a), for antidepressant capabilities by determining its metabolic profiles and comparing them to those of two reference compounds (imipramine and KW-6002). The metabolic profiles were obtained by treating male Sprague-Dawley rats with 1a and the reference compounds and subjecting them to the forced swim test. Serum and brain material was consequently collected from the animals following euthanasia, after which the metabolites were extracted and analyzed through untargeted metabolomics using both (1)H-NMR and GC-TOFMS. The current study provides insight into compound 1a’s metabolic profile. The metabolic profile of 1a was similar to those of the reference compounds. They potentially exhibit their antidepressive capabilities via downstream effects on amino acid and lipid metabolism. MDPI 2022-03-24 /pmc/articles/PMC9000263/ /pubmed/35408500 http://dx.doi.org/10.3390/molecules27072094 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Smith, Arnold Petrus
Lindeque, Jeremie Zander
van der Walt, Mietha Magdalena
Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title_full Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title_fullStr Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title_full_unstemmed Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title_short Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist
title_sort untargeted metabolomics reveals the potential antidepressant activity of a novel adenosine receptor antagonist
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000263/
https://www.ncbi.nlm.nih.gov/pubmed/35408500
http://dx.doi.org/10.3390/molecules27072094
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