An increasing number of
ACTH-related
peptides have been isolated and/or chemically synthesized. In addition to the multiplicity of molecules, there is experimental evidence for multiple target cells and multiple receptors, and hence for different
biological activities. The heptadecapeptide analogue
alsactide (
ACTH 1-17:
Synchrodyn) has a C-terminal
amide group (butylamide) and the substitution of
beta-alanine for
serine in position 1 and of
lysine for
arginine in position 17. These modifications account for enhanced
biological activity and uniquely demonstrated chronopharmacological properties. In adult healthy men, the tailoring of dosage and timing of
peptide administration was successful in a selective and transient stimulation of
glucocorticoid secretion, without a change in the plasma concentrations of
aldosterone and
testosterone. The dose of 10 micrograms
alsactide injected subcutaneously at awakening is proposed for clinical application with the aim of enhancing
cortisol secretion in diurnally active subjects. It is noteworthy that injection of even much higher doses for several days at this particular circadian stage did not elicit detectable
antibodies to the
peptide in more than 200 patients. Restoring or reinforcing the circadian ordering of bioperiodicities correlated with the adrenocortical cycle can thus be achieved as a result of a time-specified
therapy with an
ACTH-agonist analogue. The results of studies in experimental animals and of preliminary trials in human beings have emphasized the value of
alsactide as the first chronizer-
peptide in clinical medicine. Its use in the dosage here proposed is expected to be beneficial for preventing deterioration of the circadian system in the elderly, for enhancing psycho-physical performances, and for gaining compliance with regard to
chronic disease as well as tolerance to a number of potentially damaging
xenobiotics.