Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Leukotrienes vs. Montelukast – Activity, Metabolism, and Toxicity Hints for Repurposing

Version 1 : Received: 22 July 2022 / Approved: 26 July 2022 / Online: 26 July 2022 (03:27:37 CEST)

How to cite: Marques, C.F.; Marques, M.M.; Justino, G.C. Leukotrienes vs. Montelukast – Activity, Metabolism, and Toxicity Hints for Repurposing . Preprints 2022, 2022070379 (doi: 10.20944/preprints202207.0379.v1). Marques, C.F.; Marques, M.M.; Justino, G.C. Leukotrienes vs. Montelukast – Activity, Metabolism, and Toxicity Hints for Repurposing . Preprints 2022, 2022070379 (doi: 10.20944/preprints202207.0379.v1).

Abstract

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Keywords

Montelukast; Leukotrienes; Adverse drug reactions; Repurposing

Subject

LIFE SCIENCES, Biochemistry

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