[Development and pre-clinical aspects of pimecrolimus].
Pimecrolimus (SDZ ASM 981), an ascomycin derivative, inhibits the phosphatase calcineurin and blocks the production of inflammatory cytokines in T cells. In contrast to corticosteroids, pimecrolimus has a cell selective mode of action, exerting e.g. no effect on dendritic cells, which have a central function in the skin-associated immune system. Pimecrolimus shows less permeation through skin than corticosteroids and tacrolimus which indicates a lower potential for systemic side effects after topical application. In animal models pimecrolimus has a marked dose-dependent anti-inflammatory activity. However, treatment with pimecrolimus does not induce skin atrophy in contrast to corticosteroids. In contrast to tacrolimus, pimecrolimus does not impair the primary immune reaction in the sensitization phase of allergic contact dermatitis and has generally less effect on systemic immune reactions. In summary, the pharmacological profile of pimecrolimus suggests high clinical efficacy together with excellent safety.
Novartis Forschungsinstitut, Vienna, Austria. anton.stuetz@pharma.novartis.com
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Stütz
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Grassberger
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Meingassner
D000287:Administration, Topical; D000818:Animals; D001624:Betamethasone Valerate / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D051381:Rats; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D016207:Cytokines; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D001624:Betamethasone Valerate; D016559:Tacrolimus