PMID- 34987393
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220107
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World 
      Datasets and drug-gene Interaction Network.
PG  - 764279
LID - 10.3389/fphar.2021.764279 [doi]
LID - 764279
AB  - 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.
CI  - Copyright (c) 2021 Umetsu, Tanaka, Nakayama, Kato, Ueda, Nishibata, Hasegawa, 
      Matsumoto, Takeyama, Iguchi, Tanaka, Hinoi, Inagaki, Inden, Muto and Nakamura.
FAU - Umetsu, Ryogo
AU  - Umetsu R
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Tanaka, Mizuki
AU  - Tanaka M
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Nakayama, Yoko
AU  - Nakayama Y
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Kato, Yamato
AU  - Kato Y
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Ueda, Natsumi
AU  - Ueda N
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Nishibata, Yuri
AU  - Nishibata Y
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Hasegawa, Shiori
AU  - Hasegawa S
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Matsumoto, Kiyoka
AU  - Matsumoto K
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Takeyama, Noriaki
AU  - Takeyama N
AD  - Laboratory of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Iguchi, Kazuhiro
AU  - Iguchi K
AD  - Laboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Tanaka, Hiroyuki
AU  - Tanaka H
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, Gifu, Japan.
FAU - Hinoi, Eiichi
AU  - Hinoi E
AD  - Laboratory of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, Gifu, Japan.
FAU - Inagaki, Naoki
AU  - Inagaki N
AD  - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu 
      University, Gifu, Japan.
FAU - Inden, Masatoshi
AU  - Inden M
AD  - Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Muto, Yoshinori
AU  - Muto Y
AD  - Department of Functional Bioscience, Gifu University School of Medicine, Gifu, 
      Japan.
FAU - Nakamura, Mitsuhiro
AU  - Nakamura M
AD  - Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
LA  - eng
PT  - Journal Article
DEP - 20211220
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8720925
OTO - NOTNLM
OT  - drug-gene intraction
OT  - enrichment analysis
OT  - food and drug administration adverse event reporting system
OT  - montelukast
OT  - neuropsychiatric adverse events
OT  - protein-protein interaction
COIS- 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.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/12/20
CRDT- 2022/01/06 05:52
PHST- 2021/08/25 00:00 [received]
PHST- 2021/11/22 00:00 [accepted]
PHST- 2022/01/06 05:52 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/12/20 00:00 [pmc-release]
AID - 764279 [pii]
AID - 10.3389/fphar.2021.764279 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Dec 20;12:764279. doi: 10.3389/fphar.2021.764279. 
      eCollection 2021.