THE BIOLOGICAL ACTIVITY OF [1-D-SERINE, 17–18-DILYSINE]-β-CORTICOTROPHIN-(1-18)-OCTADECAPEPTIDE-AMIDE

Abstract

ABSTRACT Compared with β-corticotrophin-(1-24)-tetracosapeptide (tetracosactide), [1-D-serine,17,18-dilysine]-β-corticotrophin-(1-18)-octadecapeptide-amide (CIBA 41,795-Ba) is a highly potent peptide in respect of its adrenal and extra-adrenal activities in the rat. The adrenal steroidogenic activity of these two peptides in vivo varies according to the parameter measured. A comparison of the threshold doses reveals that 41,795-Ba is 10 times more potent than tetracosactide, but when the doses producing equal areas under the time-curves are compared, 41,795-Ba is 100 times more potent, while the duration of action of 41,795-Ba expressed in terms of the maximum plasma corticosterone concentrations is 4 times longer than that of the same dose of tetracosactide. The octadecapeptide is about 10 times more potent than tetracosactide in its capacity to evoke steroidogenesis in vitro, in depleting the adrenals of ascorbic acid, and in its melanophore-expanding activity. Its lipolytic potency is about 3 times greater than that of tetracosactide in vitro and about 100 times greater in vivo at threshold doses. Preliminary studies in man have shown that 41,795-Ba possesses about 10 times the corticotrophic activity of tetracosactide and a longer duration of action.