Abstract

In a previous series of 22-day evaluations of 31 compounds, only corticosterone-21-acetate (C-21-A) increased righting ability of genetically dystrophic chickens to a greater extent than the standard of comparison, methysergide maleate. In the present study, C-21-A was subjected to longer-term trials of up to 48 days, and additional signs of the myopathy were examined. The highest doses of C-21-A increased righting ability for the duration of the trials, decreased the typically elevated plasma levels of creatine kinase (CK) activity by more than 80%, and improved morphology of the dystrophic pectoralis major muscle at the light microscopic level. The major adverse effect of C-21-A, reduction of body weight, was consistently observed at the relatively high doses needed to increase righting ability. That alone, however, could not account for increased righting ability, and plasma CK activity was decreased even at doses that did not reduce body weight. The results show that C-21-A is the most effective compound yet tested in this system and, perhaps more significantly, provides the first evidence that it is possible to identify compounds that improve muscle morphology in a hereditary myopathy using a short-term, step-wise system.

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