• Jorge Carlos Santos da Costa, Priscilla Christina Olsen, Rodrigo de Azeredo Siqueira, Vinícius de Frias Carvalho, Magda Fraguas Serra, Luiz Anastácio Alves, Robson Xavier Faria, Debora Gonçalves Xisto, Rocco Patricia Rieken Macêdo PR, Renato Sérgio Balão Cordeiro, Patrícia Machado Rodrigues E Silva, and Marco Aurélio Martins.
• Department of Physiology and Pharmacodynamics, IOC, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
• J. Allergy Clin. Immunol. 2007 Jan 1; 119 (1): 219-25.

BackgroundPrior reports show that nebulized lidocaine might be an effective treatment for asthma.ObjectiveWe 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.MethodsBlockade of Na(+) currents was assayed in cultured GH(3) 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.ResultsThe 50% inhibitory concentration values for blockade of Na(+) 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.ConclusionReplacement 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 ImplicationsNebulized JMF2-1 might be a means of achieving the antiasthmatic effects of lidocaine without the anesthetic effects.

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