JM25-1, a Lidocaine Analog Combining Airway Relaxant and Antiinflammatory Properties: Implications for New Bronchospasm Therapy

dc.creatorSerra, Magda F.
dc.creatorNeves, Josiane S.
dc.creatorCouto, Gina C.
dc.creatorCotias, Amanda C.
dc.creatorPão, Camila R.
dc.creatorOlsen, Priscilla C.
dc.creatorCarvalho, Katharinne I. Moraes de
dc.creatorAnjos Valotta, Edna A.
dc.creatorFaria, Robson X.
dc.creatorCosta, Jorge C. S.
dc.creatorCordeiro, Renato S. B.
dc.creatorSilva, Patricia M. R.
dc.creatorMartins, Marco A.
dc.date2016-07-12T23:20:10Z
dc.date2016-07-12T23:20:10Z
dc.date2016
dc.date.accessioned2023-09-26T22:12:58Z
dc.date.available2023-09-26T22:12:58Z
dc.identifierSERRA, Magda F, et al. JM25-1, a Lidocaine Analog Combining Airway Relaxant and Antiinflammatory Properties: Implications for New Bronchospasm Therapy. Anesthesiology, v.124, p.109-20, 2016.
dc.identifier0003-3022
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/14832
dc.identifier1528-1175
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8876368
dc.descriptionBackground: Inhaled lidocaine antagonized bronchospasm in animal models and patients, but adverse effects limited its efficacy. This study evaluated the antibronchospasm potential of the analog JM25-1, exploring in vitro mechanisms and translation to an animal model. Methods: The effectiveness of JM25-1 was assessed in GH3 cells, rat tracheal rings, mouse lymphocytes, and human eosinophil systems in vitro, assessing changes in Na+ current, contraction, proliferation, and survival, respectively. Lung function and inflammatory changes were studied in ovalbumin-sensitized mice. Results: The efficacy of JM25-1 was higher than lidocaine in inhibiting carbachol-induced and calcium-induced tracheal contractions (maximum effect inhibition at 1 mM [%]: 67 ± 10 [JM25-1] vs. 41 ± 11 [lidocaine] [P < 0.001] for carbachol; 100 ± 3 [JM25-1] vs. 36 ± 26 [lidocaine] [P < 0.001] for Ca2+; mean ± SD; n = 9 each) but lower in Na+ current (50% inhibitory concentration = 151.5, n = 8 vs. 0.2 mM; n = 5; P < 0.001). JM25-1 also inhibited eosinophil survival (dead cells [%]: 65 ± 6; n = 4; P < 0.001 at 1 mM) and lymphocyte proliferation (cells in phase S + G2 [%]: 94 ± 10; n = 6; P < 0.001) at 0.6 mM. Aerosolized JM25-1 (1%) decreased lung eosinophil numbers from 13.2 ± 2.4 to 1.7 ± 0.7 × 104/μm2 (n = 6; P < 0.001) and neutrophils from 1.9 ± 0.4 to 0.2 ± 0.1 × 104/μm2 (n = 7; P < 0.001). Other parameters, including airway hyperreactivity, cytokines, mucus, and extracellular matrix deposition, were also sensitive to aerosolized JM25-1. Conclusion: These findings highlight the potential of JM25-1, emphasizing its putative value in drug development for clinical conditions where there is bronchospasm.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherLippincott, Williams & Wilkins:
dc.rightsrestricted access
dc.subjectEspasmo Brônquico
dc.subjectLidocaína
dc.subjectRelaxante das vias aéreas
dc.subjectPropriedades anti-inflamatórias
dc.subjectBronchospasm
dc.subjectLidocaine
dc.subjectJM25-1
dc.subjectAirway relaxant
dc.subjectAntiinflammatory Properties
dc.titleJM25-1, a Lidocaine Analog Combining Airway Relaxant and Antiinflammatory Properties: Implications for New Bronchospasm Therapy
dc.typeArticle


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