Peptide enhancement of neuromuscular function: animal and clinical studies

Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons.