Atopic dermatitis-like symptoms in hypomagnesaemic hairless rats are prevented and inhibited by systemic or topical SDZ ASM 981.
Magnesium deficiency in hairless rats results in a transient erythematous rash within several days, the pathogenetic mechanisms of which are not yet well defined. However, the extremely pruritic rash closely mimics the acute clinical features of atopic dermatitis. Owing to the similarity of clinical signs between hypomagnesaemic rats and patients with atopic dermatitis, this rodent skin condition holds promise as a model for the in vivo evaluation of new treatment modalities against pruritic inflammatory skin conditions. The efficacy of the new ascomycin macrolactam derivative SDZ ASM 981 was tested in hypomagnesaemic rats by systemic or topical administration using prophylactic or therapeutic treatment regimens. Oral treatment of diseased rats with SDZ ASM 981 (12.5 mg kg-1 daily) inhibited the erythematous pruritic rash within 1 day after the start of treatment. This was associated with a clear reduction in histaminaemia, leucocytosis, eosinophilia and serum nitric oxide levels. The same daily oral dose of SDZ ASM 981 administered before the onset of the rash proved to be an efficacious prophylactic treatment regimen to prevent signs. Topical treatment of the ears with 0.4% SDZ ASM 981 locally inhibited and prevented inflammatory changes in a therapeutic and prophylactic treatment regimen, respectively. The histo- and immunopathological skin changes, as well as the numbers of degranulated mast cells in the dermis, were reversed towards normal after oral and topical administration. The pharmacological activity of SDZ ASM 981 reported here corresponds well to its anti-inflammatory and antipruritic activity observed in atopic dermatitis patients, confirming the usefulness of this rat model in drug evaluations.
Neckermann
G
G
Novartis Research Institute, Brunner Strasse 59, A-1235 Vienna, Austria.
Bavandi
A
A
Meingassner
J G
JG
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D003876:Dermatitis, Atopic / Q000209:etiology / Q000517:prevention & control*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D008275:Magnesium Deficiency / Q000150:complications* / Q000188:drug therapy; D008297:Male; D051381:Rats; D011923:Rats, Nude; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
D003879:Dermatologic Agents; C117268:pimecrolimus; D016559:Tacrolimus