EFFECTS OF CALMODULIN ANTAGONISTS AND ANESTHETICS ON THE SKIN-LESIONSINDUCED BY 2-CHLOROETHYLETHYL SULFIDE

\The effects of calmodulin antagonists and anesthetics on the skin les ions induced by an alkylating vesicant, 2-chloroethylethyl sulfide, we re investigated using female hairless mice. 2-Chloroethylethyl sulfide , topically applied (0.6 mu l/5 mm in diameter) on the back skin of ha irless mice, induced mild to moderate petechiae on the Ist day, and ul cers with a thick scab after 3 days. The healing process started after 6 days, resulting in shedding of scabs on 9.52 days. Water-soluble oi ntment bases showed some beneficial effects, whereas oily bases made t he skin lesions worse. Trifluoperazine (0.5-1%) and thioridazine (2%), potent calmodulin antagonists, in Pluronic F-127 base substantially p revented the development of 2-chloroethylethyl sulfide-induced skin le sions. A similar effect was achieved with pentamidine (10%), another t ype of calmodulin antagonist, but not with ketoconazole, a weak calmod ulin antagonist. In addition, anesthetics, such as lidocaine and pento barbital, showed some protection, although at high concentrations (> 5 %). As judged by the microscopic appearance, trifluoperazine successfu lly reduced the hemorrhage and the infiltration of inflammatory cells in early skin lesions, and the formation of thick scabs, which leads t o granulomatous scar tissue in late lesions. These results suggest tha t some calmodulin antagonists and anesthetics in water-soluble bases m ight be a choice for the treatment of 2-chloroethylethyl sulfide-induc ed skin burns.