ACTH/MSH(4-10) ANALOG BIM-22015 AIDS REGENERATION VIA NEUROTROPHIC AND MYOTROPHIC ATTRIBUTES

Structural differences between noncorticotropic ACTH peptides result in marked differences in their effects on regenerating nerve and muscle in rats. The ACTH/MSH(4-10) analog BIM 22015 was administered IP in dosages from 0.1 to 40 mug/kg/48 h for 5, 7, or 11 days after peroneal nerve crush, and characteristics of extensor digitorum longus (EDL) muscle were studied and compared with ACTH/MSH(4-10). Eleven days postcrush 40 mug/kg BIM 22015 increases rate of development of tetanic tension and amplitude of contraction of indirectly stimulated EDL. In a 21-day study, reinnervated BIM 22015-treated muscles retain tetanic strength, whereas ACTH/MSH(4-10)-treated muscles are significantly weakened. Both peptides show neurotrophic characteristics in their stimulation of endplate nerve terminal branching. However, in contrast to ACTH/MSH(4-10), BIM 22015 also prevents denervation atrophy of the EDL. This dual neurotrophic and myotrophic role for BIM 22015 accords it a clinical potential for degenerative myopathies of either pure or mixed origin, such as muscular dystrophy, infantile spinal atrophy, and hypotonia.