JMF2-1, a lidocaine derivative acting on airways spasm and lung allergic inflammation in rats Jorge Carlos Santos da Costa, PhD, Priscilla Christina.

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JMF2-1, a lidocaine derivative acting on airways spasm and lung allergic inflammation in rats Jorge Carlos Santos da Costa, PhD, Priscilla Christina Olsen, BSc, Rodrigo de Azeredo Siqueira, MD, MSc, Vinícius de Frias Carvalho, PhD, Magda Fraguas Serra, PhD, Luiz Anastácio Alves, PhD, Robson Xavier Faria, MSc, Debora Gonçalves Xisto, MSc, Patricia Rieken Macêdo Rocco, MD, PhD, Renato Sérgio Balão Cordeiro, PhD, Patrícia Machado Rodrigues e Silva, PhD, Marco Aurélio Martins, PhD Journal of Allergy and Clinical Immunology Volume 119, Issue 1, Pages 219-225 (January 2007) DOI: 10.1016/j.jaci.2006.08.037 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Local anesthesia activity and whole-cell recording of Na+ channel currents. A, Duration to full recovery of sensory block (mean ± SD, n = 6) after intradermal injection of increasing doses of lidocaine (open circles) and JMF2-1 (solid circles) in rats. ∗P < .05 compared with lidocaine-treated group. B, Tonic block of Na+ currents in GH3 cells by lidocaine (open circles) and JMF2-1 (solid circles). Data are reported as the means ± SD (n = 6 for all groups, with at least 3 independent experiments). Journal of Allergy and Clinical Immunology 2007 119, 219-225DOI: (10.1016/j.jaci.2006.08.037) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Histamine release inhibition. Blockade of allergen-evoked tissue histamine release caused by treatment with increasing concentrations of either lidocaine (open circles) or JMF2-1 (solid circles). Values are expressed as means ± SD from at least 4 experiments. Journal of Allergy and Clinical Immunology 2007 119, 219-225DOI: (10.1016/j.jaci.2006.08.037) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Ex vivo tracheal spasm blockade. Inhibitory effect of lidocaine (A), JMF2-1 (B), and albuterol (C) on the anaphylactic contraction evoked by ovalbumin (100 μg/mL) in rat tracheas. Values are expressed as means ± SD from at least 6 experiments. ∗P < .05 compared with the untreated group; +P < .05 compared with the lidocaine-treated group. Journal of Allergy and Clinical Immunology 2007 119, 219-225DOI: (10.1016/j.jaci.2006.08.037) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Interference on the Ca2+-tension relationship. Effect of lidocaine (A) and JMF2-1 (B) at concentrations of zero (squares), 0.1 mmol/L (circles), and 1 mmol/L (triangles) on the contraction development induced by changes in extracellular Ca2+ during 100 mM K+ depolarization. Values are expressed as means ± SEM from at least 4 experiments. ∗P <. 05 compared with the untreated group; +P < .05 compared with the 0.1 mmol/L JMF2-1–treated group. Journal of Allergy and Clinical Immunology 2007 119, 219-225DOI: (10.1016/j.jaci.2006.08.037) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Lung tissue leukocytes. Effect of lidocaine (left-hatched columns) and JMF2-1 (right-hatched columns) on total leukocytes (A), mononuclear cells (B), eosinophils (C), and neutrophils (D) infiltrated in the lung tissue of sensitized and ovalbumin-challenged rats. Values are expressed as means ± SEM from at least 6 animals. +P < .05 compared with the sensitized, saline-challenged group (open columns); ∗P < .05 compared with the ovalbumin-challenged and saline-treated group (closed columns). Journal of Allergy and Clinical Immunology 2007 119, 219-225DOI: (10.1016/j.jaci.2006.08.037) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions