Author | Costa, Jorge Carlos Santos da | |
Author | Olsen, Priscilla Christina | |
Author | Siqueira, Rodrigo de Azeredo | |
Author | Carvalho, Vinícius de Frias | |
Author | Serra, Magda Fraguas | |
Author | Alves, Luiz Anastácio | |
Author | Faria, Robson Xavier | |
Author | Xisto, Debora Gonçalves | |
Author | Rocco, Patricia Rieken Macêdo | |
Author | Cordeiro, Renato Sérgio Balão | |
Author | Silva, Patrícia Machado Rodrigues e | |
Author | Martins, Marco Aurélio | |
Access date | 2020-03-30T21:07:22Z | |
Available date | 2020-03-30T21:07:22Z | |
Document date | 2007 | |
Citation | COSTA, Jorge Carlos Santos da et al. JMF2-1, a lidocaine derivative acting on airways spasm and lung allergic inflammation in rats. Journal of Allergy and Clinical Immunology, v. 119, n. 1, p. 219-225, Jan. 2007. | pt_BR |
ISSN | 0091-6749 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/40571 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Asma | pt_BR |
Subject in Portuguese | Anestésicos locais | pt_BR |
Subject in Portuguese | Lidocaína | pt_BR |
Subject in Portuguese | Modelo de rato | pt_BR |
Title | JMF2-1, a lidocaine derivative acting on airways spasm and lung allergic inflammation in rats | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.jaci.2006.08.037 | |
Abstract | Background: Prior reports show that nebulized lidocaine might be an effective treatment for asthma. Objective: We sought to determine the anti-inflammatory and spasmolytic effects of lidocaine and its analogue, JMF2-1,
which we have synthesized for reduced local anesthetic activity. Methods: Blockade of Na1 currents was assayed in cultured GH3 cells by using the patch-clamp technique, whereas anesthesia was assessed in a cutaneous pinching test in rats. Lidocaine and its analogue were nebulized into sensitized rats for evaluation of their effectiveness on airways spasm and
inflammation induced by methacholine and allergen, respectively. Tissue histamine release and tracheal spasm triggered by allergen challenge in the absence and presence of these treatments were also examined in vitro.
Results: The 50% inhibitory concentration values for blockade of Na1 currents after treatment with JMF2-1 (25.4 mM) was remarkably higher than that of lidocaine (0.18 mM), which is consistent with the weak anesthetic capacity of this analogue. In contrast, JMF2-1 was more potent than lidocaine in inhibiting allergen-induced histamine release and tracheal spasm. In in vivo settings methacholine-induced increase in lung resistance (145%) significantly reduced to 72% and 47% after lidocaine and JMF2-1 treatment, respectively. Both treatments inhibited by about 81% allergen-evoked eosinophil accumulation into the lung tissue. Conclusion: Replacement of the 2,6-dimethyl radicals by the 2-trifluormethyl group on the benzene ring of lidocaine significantly reduces anesthetic activity, preserving its ability to prevent key aspects of the allergic inflammatory response in the lung. Clinical implications: Nebulized JMF2-1 might be a means of achieving the antiasthmatic effects of lidocaine without the anesthetic effects. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Farmanguinhos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Asthma | pt_BR |
Subject | Local anesthetics | pt_BR |
Subject | Lidocaine | pt_BR |
Subject | Rat model | pt_BR |
e-ISSN | 1097-6825 | |
Embargo date | 2025-01-01 | |