Pharmacological profiling of JME-173, a novel mexiletine derivative combining dual anti-inflammatory/anti-spasmodic functions and limited action in Na+ channels

Pinto, Douglas Pereira; Coutinho, Diego de Sá; Carvalho, Katharinne Ingrid Moraes de; Ferrero, Maximiliano Ruben; Silva, Letícia Vallim da; Silveira, Gabriel Parreiras Estolano da; Silva, Diego Medeiros da; Araújo, João Felipe Garcia; Silva, Aline C.A.; Pereira, Heliana Martins; Fonseca, Laís Bastos da; Faria, Robson Xavier; Souza, Marcus V. N. de; Silva, Emerson Teixeira da; Santos-Filho, Osvaldo A.; Costa, Jorge; Amendoeira, Fábio Coelho; Martins, Marco A.

doi:10.1016/j.ejphar.2020.173367

Cited by 2 publications

(2 citation statements)

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“…Female C57BL/6 mice weighing 18–20 g and 8–10 weeks old were exposed to Cs from 12 commercial full-flavored Marlboro cigarettes (10 mg tar, 0.9 mg nicotine, and 10 mg monoxide) per day or ambient air (controls) for 11 days, using a smoking chamber as described previously [ 49 ]. On the 7th day of exposure, animals were anesthetized with 50 µL s.c. of ketamine (60 mg/Kg) and xylazine (4 mg/Kg) solution and infected with 1000 pfu of influenza (H1N1) virus strain A/PR/8/34 H1N1 intranasally.…”

Section: Methodsmentioning

confidence: 99%

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

et al. 2021

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Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.

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Section: Methodsmentioning

confidence: 99%

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

et al. 2021

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“…Weigh Mexiletine 1mg and dilute in 1ml organic solvent so that the concentration is linear at all parts for 1µg per µl and this solution is used for sample processing and its (Olszowy et al, 2010) also must be maintained and stored at -2 0 C to -10 0 C in glass lasks. HQC -Highest quality control is the highest point at the calibration curve (Pinto et al, 2020).…”

Section: Preparation Standard Solutionsmentioning

confidence: 99%

Estimation and Evaluation of Mexiletine for Bio-availability and Bio-equivalence studies by Liquid phase extraction using LC-MS/MS

Elavarasi¹,

Cherian²,

Shanmugasundaram³

et al. 2021

ijrps

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The work aims to develop an appropriate method for mexiletine with 35-65% recovery by the LPE method with efficient and selective efficacy of the IS and analyte for the analysis under Liquid Chromatography-Mass Spectrometry/ Mass Spectrometry. This method also reveals the bio-availability and bio-equivalence report for Internal Standard & working standard. At first, the selection of proper IS. The Internal standard should be structurally more similar to mexiletine. The selection of method plays a major role in which extraction procedure is done either by LPE or SPE. The selection of separation procedure should be either isocratic or gradient. Selection of column on bases separation principle of the compound. Since separation is the major principle for chromatography. Argon and Nitrogen Gas is used as carries with a flow-rate of 2L min. Temperature at 20°C, the pressure at 20psi. If the instrument doesn't show any peak or response in after loading sample, check the columns is an aqueous or reverse-phase and then submit the sample. Check all the solution and column and temperature and system stability before loading the sample. After loading the sample, must form calibration curve it must form linearity. The method found should possess the following parameters Specific & Selectivity, Precision & Accuracy. The work aims to develop a simple, elegant way for quantification of a molecule and the method determined will have recovery of 35-65% worldwide. This quantification will be further utilized in Full-Method Validation.

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Pharmacological profiling of JME-173, a novel mexiletine derivative combining dual anti-inflammatory/anti-spasmodic functions and limited action in Na+ channels

Cited by 2 publications

References 29 publications

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

Estimation and Evaluation of Mexiletine for Bio-availability and Bio-equivalence studies by Liquid phase extraction using LC-MS/MS

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