Several Different Ion Channel Modulators Abrogate Contact Hypersensitivity in Mice

A major obstacle in transdermal delivery of drugs is the development of adverse skin sensitization reactions. We tested the concept that ion channel modulators as a class of agents suppress contact hypersensitivity in a mouse model. Mice were sensitized to several contact sensitizing chemicals including dinitrochlorobenzene (DNCB) and a sensitizing drug, nadolol. We report our successful use of several ion channel modulators in suppressing contact hypersensitivity, including amiloride, ethacrynic acid (ECA), nifedipine and verapamil. For this purpose, Balb/c female mice were sensitized with DNCB, and abrogation of induction of contact hypersensitivity reaction (CHR) was examined by topical pretreatment of the target-sensitized skin with amiloride, nifedipine and pairwise combinations of these agents with ECA, a potassium ion channel blocker. Abrogation of induction of CHR was observed in all cases. In addition, suppression of contact hypersensitivity was observed in nadolol-sensitized mice pretreated with either verapamil or nifedipine. The results indicate that ion channel inhibitors are broadly effective inhibitors of allergic contact dermatitis and may be useful for facilitating the transdermal delivery of therapeutic drugs that have sensitization potential.