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.
|Titolo:||Alsactide : ACTH-agonist for use in microdoses in brain-adrenal and other feedsidewards|
CARANDENTE, FRANCA (Secondo)
MARTINI, LUCIANO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||1987|
|Appare nelle tipologie:||01 - Articolo su periodico|