A potent agonist of GPR35 and a mast cell stabilizer
Lodoxamide is a potent agonist of GPR35 with an EC50 value of 1.61 nM in a β-arrestin-2 interaction assay using CHO-K1 cells expressing the human receptor.1 It inhibits histamine release induced by compound 48/80 , anti-IgE, or A23187 in isolated rat peritoneal mast cells (IC50s = 0.1-50 ?M) and inhibits A23187-induced calcium influx in mast cells.2 It reduces antigen-induced histamine release from rat conjunctival tissue by 46% in vitro when used at a concentration of 10 ?g/ml.3 Lodoxamine (0.1 and 10%, w/v) reduces the immediate hypersensitivity response in rat conjunctiva in vivo in a dose-dependent manner and reduces mast cell degranulation in a topical ovalbumin challenge.3,4 Formulations containing lodoxamide have been used in the treatment of vernal conjunctivitis and keratitis.
1.MacKenzie, A.E., Caltabiano, G., Kent, T.C., et al.The antiallergic mast cell stabilizers lodoxamide and bufrolin as the first high and equipotent agonists of human and rat GPR35Mol. Pharmacol.85(1)91-104(2014) 2.Johnson, H.G., and Sheridan, A.Q.The characterization of lodoxamide, a very active inhibitor of mediator release, in animal and human models of asthmaAgents Actions18(3-4)301-305(1986) 3.Yanni, J.M., Weimer, L.K., Glaser, R.L., et al.Effect of lodoxamide on in vitro and in vivo conjunctival immediate hypersensitivity responses in ratsInt. Arch. Allergy. Immunol.101(1)102-106(1993) 4.Bayer, A., Uluda?, H.A., Sobaci, G., et al.Comparison of antiallergic drugs in an experimental model of ocular anaphylaxisOphthalmologica217(2)119-123(2003)
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