Montelukast: The New Therapeutic Option for the Treatment of Epilepsy

Tesfaye, Bekalu Amare; Hailu, Haftom Gebregergs; Zewdie, Kaleab Alemayehu; Ayza, Muluken Altaye; Berhe, Derbew Fikadu

doi:10.2147/jep.s277720

Cited by 8 publications

(11 citation statements)

References 64 publications

(49 reference statements)

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“…Montelukast, an anti-asthmatic drug is a leukotriene receptor antagonist (LTA) that counteracts in ammation and other detrimental pathways that are linked with other neurodegenerative diseases and allergic rhinitis may be protective or risky in nature 91 .The evidence for adverse neuropsychiatric outcomes associated with LTAs is inconclusive. Current controlled clinical trials have reported mild to infrequent adverse effects, which is indicative of montelukast being a safe and well tolerated medication.…”

Section: Montelukastmentioning

confidence: 99%

DeepBiomarker2: Prediction of alcohol and substance use disorder risk in post-traumatic stress disorder patients using electronic medical records and multiple social determinants of health

Miranda

Fan

et al. 2023

Preprint

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Introduction: Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. In our previous study, we developed a deep learning-based model, DeepBiomarker by utilizing electronic medical records (EMR) to predict the outcomes of patients with suicide-related events in post-traumatic stress disorder (PTSD) patients. Methods We improved our deep learning model to develop DeepBiomarker2 through data integration of multimodal information: lab tests, medication use, diagnosis, and social determinants of health (SDoH) parameters (both individual and neighborhood level) from EMR data for outcome prediction. We further refined our contribution analysis for identifying key factors. We applied DeepBiomarker2 to analyze EMR data of 38,807 patients from University of Pittsburgh Medical Center diagnosed with PTSD to determine their risk of developing alcohol and substance use disorder (ASUD). Results DeepBiomarker2 predicted whether a PTSD patient will have a diagnosis of ASUD within the following 3 months with a c-statistic (receiver operating characteristic AUC) of 0·93. We used contribution analysis technology to identify key lab tests, medication use and diagnosis for ASUD prediction. These identified factors imply that the regulation of the energy metabolism, blood circulation, inflammation, and microbiome is involved in shaping the pathophysiological pathways promoting ASUD risks in PTSD patients. Our study found protective medications such as oxybutynin, magnesium oxide, clindamycin, cetirizine, montelukast and venlafaxine all have a potential to reduce risk of ASUDs. Discussion DeepBiomarker2 can predict ASUD risk with high accuracy and can further identify potential risk factors along with medications with beneficial effects. We believe that our approach will help in personalized interventions of PTSD for a variety of clinical scenarios.

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Section: Montelukastmentioning

confidence: 99%

DeepBiomarker2: Prediction of alcohol and substance use disorder risk in post-traumatic stress disorder patients using electronic medical records and multiple social determinants of health

Miranda

Fan

et al. 2023

Preprint

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“…CREB inhibition in these cells via the H89 pharmacological inhibitor prevents montelukast-induced PGC-1α upregulation ( Wang et al, 2019b ). Moreover, montelukast is neuroprotective in young children and adults with brain tumors, traumatic brain injury, brain ischemia, and epilepsy but has not been tested in infants with WMI ( Biber et al, 2009 ; Rupprecht et al, 2014 ; Eriksson et al, 2018 ; Fatima et al, 2019 ; Tesfaye et al, 2021 ). Overall, montelukast is a low-risk drug that has been used in infants and children of various ages with no significant adverse effects reported.…”

Section: Therapeutic Agents That Can Regulate Pgc-1α Activitymentioning

confidence: 99%

PGC-1α activity and mitochondrial dysfunction in preterm infants

2022

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Extremely low gestational age neonates (ELGANs) are born in a relatively hyperoxic environment with weak antioxidant defenses, placing them at high risk for mitochondrial dysfunction affecting multiple organ systems including the nervous, respiratory, ocular, and gastrointestinal systems. The brain and lungs are highly affected by mitochondrial dysfunction and dysregulation in the neonate, causing white matter injury (WMI) and bronchopulmonary dysplasia (BPD), respectively. Adequate mitochondrial function is important in providing sufficient energy for organ development as it relates to alveolarization and axonal myelination and decreasing oxidative stress via reactive oxygen species (ROS) and reactive nitrogen species (RNS) detoxification. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a master regulator of mitochondrial biogenesis and function. Since mitochondrial dysfunction is at the root of WMI and BPD pathobiology, exploring therapies that can regulate PGC-1α activity may be beneficial. This review article describes several promising therapeutic agents that can mitigate mitochondrial dysfunction through direct and indirect activation and upregulation of the PGC-1α pathway. Metformin, resveratrol, omega 3 fatty acids, montelukast, L-citrulline, and adiponectin are promising candidates that require further pre-clinical and clinical studies to understand their efficacy in decreasing the burden of disease from WMI and BPD in preterm infants.

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“… 1 , 2 There is also increasing interest in repositioning montelukast for treating various other health conditions. 3 , 4 , 5 , 6 …”

Section: Introductionmentioning

confidence: 99%

“…1,2 There is also increasing interest in repositioning montelukast for treating various other health conditions. [3][4][5][6] The evidence base for adverse neuropsychiatric outcomes associated with LTMAs is mixed and inconclusive. 7 Nevertheless, in 2020, the US Food and Drug Administration (FDA) issued a new warning about potential serious mental health outcomes associated with montelukast to promote further awareness of potential adverse effects and also advised reducing montelukast's use in the treatment of allergic rhinitis.…”

Section: Introductionmentioning

confidence: 99%