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Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network

Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food...

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Autores principales: Umetsu, Ryogo, Tanaka, Mizuki, Nakayama, Yoko, Kato, Yamato, Ueda, Natsumi, Nishibata, Yuri, Hasegawa, Shiori, Matsumoto, Kiyoka, Takeyama, Noriaki, Iguchi, Kazuhiro, Tanaka, Hiroyuki, Hinoi, Eiichi, Inagaki, Naoki, Inden, Masatoshi, Muto, Yoshinori, Nakamura, Mitsuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720925/
https://www.ncbi.nlm.nih.gov/pubmed/34987393
http://dx.doi.org/10.3389/fphar.2021.764279
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author Umetsu, Ryogo
Tanaka, Mizuki
Nakayama, Yoko
Kato, Yamato
Ueda, Natsumi
Nishibata, Yuri
Hasegawa, Shiori
Matsumoto, Kiyoka
Takeyama, Noriaki
Iguchi, Kazuhiro
Tanaka, Hiroyuki
Hinoi, Eiichi
Inagaki, Naoki
Inden, Masatoshi
Muto, Yoshinori
Nakamura, Mitsuhiro
author_facet Umetsu, Ryogo
Tanaka, Mizuki
Nakayama, Yoko
Kato, Yamato
Ueda, Natsumi
Nishibata, Yuri
Hasegawa, Shiori
Matsumoto, Kiyoka
Takeyama, Noriaki
Iguchi, Kazuhiro
Tanaka, Hiroyuki
Hinoi, Eiichi
Inagaki, Naoki
Inden, Masatoshi
Muto, Yoshinori
Nakamura, Mitsuhiro
author_sort Umetsu, Ryogo
collection PubMed
description Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3–22.9) and 8.2 (95% CI: 7.8–8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of “neuroactive ligand–receptor interaction.” “Mood disorders” and “major depressive disorder” were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.
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spelling pubmed-87209252022-01-04 Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network Umetsu, Ryogo Tanaka, Mizuki Nakayama, Yoko Kato, Yamato Ueda, Natsumi Nishibata, Yuri Hasegawa, Shiori Matsumoto, Kiyoka Takeyama, Noriaki Iguchi, Kazuhiro Tanaka, Hiroyuki Hinoi, Eiichi Inagaki, Naoki Inden, Masatoshi Muto, Yoshinori Nakamura, Mitsuhiro Front Pharmacol Pharmacology Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3–22.9) and 8.2 (95% CI: 7.8–8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of “neuroactive ligand–receptor interaction.” “Mood disorders” and “major depressive disorder” were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms. Frontiers Media S.A. 2021-12-20 /pmc/articles/PMC8720925/ /pubmed/34987393 http://dx.doi.org/10.3389/fphar.2021.764279 Text en Copyright © 2021 Umetsu, Tanaka, Nakayama, Kato, Ueda, Nishibata, Hasegawa, Matsumoto, Takeyama, Iguchi, Tanaka, Hinoi, Inagaki, Inden, Muto and Nakamura. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Umetsu, Ryogo
Tanaka, Mizuki
Nakayama, Yoko
Kato, Yamato
Ueda, Natsumi
Nishibata, Yuri
Hasegawa, Shiori
Matsumoto, Kiyoka
Takeyama, Noriaki
Iguchi, Kazuhiro
Tanaka, Hiroyuki
Hinoi, Eiichi
Inagaki, Naoki
Inden, Masatoshi
Muto, Yoshinori
Nakamura, Mitsuhiro
Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title_full Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title_fullStr Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title_full_unstemmed Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title_short Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
title_sort neuropsychiatric adverse events of montelukast: an analysis of real-world datasets and drug−gene interaction network
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720925/
https://www.ncbi.nlm.nih.gov/pubmed/34987393
http://dx.doi.org/10.3389/fphar.2021.764279
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