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. 2021 Dec 20:12:764279.
doi: 10.3389/fphar.2021.764279. eCollection 2021.

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

Ryogo Umetsu  1 , Mizuki Tanaka  1 , Yoko Nakayama  1 , Yamato Kato  1 , Natsumi Ueda  1 , Yuri Nishibata  1 , Shiori Hasegawa  1 , Kiyoka Matsumoto  1 , Noriaki Takeyama  2 , Kazuhiro Iguchi  3 , Hiroyuki Tanaka  4 , Eiichi Hinoi  2   4 , Naoki Inagaki  4 , Masatoshi Inden  5 , Yoshinori Muto  6 , Mitsuhiro Nakamura  1
Affiliations

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

Ryogo Umetsu et al. Front Pharmacol. .

Abstract

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.

Keywords: drug-gene intraction; enrichment analysis; food and drug administration adverse event reporting system; montelukast; neuropsychiatric adverse events; protein-protein interaction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Top four gene interaction networks based on the MCODE plug-in of Cytoscape.
FIGURE 2
FIGURE 2
Dot plot of KEGG functional enrichment analysis.
FIGURE 3
FIGURE 3
Dot plot of DisGeNET disease enrichment analysis.
See this image and copyright information in PMC

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