Ноотропные и анксиолитические эффекты гептапептида АКТГ 6-9 Pro-Gly-Pro

Abstract

Melanocortins (MCs) have a wide spectrum of physiological activity. All native MCs have a core pharmacophore structure of tetrapeptide His-Phe-Arg-Trp sequence, corresponding to ACTH6-9 fragment. The sequence is necessary for activation of all subtypes of MC receptors, but the tetrapeptide has poor potency and selectivity. It was shown earlier that the addition of proline-rich sequences to natural peptides led to enhancing and prolongation of their neurotropic effects. An example of such a compound is fragment ACTH4-10 analog with prolong neurotropic effects heptapeptide Semax (ACTH4-7Pro-Gly-Pro). The work is devoted to the research of the effects of a synthetic peptide comprising the natural ACTH6-9 sequence and the fragment PGP in its structure – ACTH6-9PGP (HFRWPGP). The peptide effects on the learning ability and anxiety level were studied in white rats. The peptide was injected intranasally at a dose of 0.05 mg/kg 15 min or 20 h before the experiment. It was shown that heptapeptide ACTH6-9PGP improved the acquisition of food-motivated maze task and retention of passive avoidance task, and also it exhibited an anxiolytic activity in elevated plus maze test when injected 15 min before testing. The peptide administration 20 h before testing did not lead to changes in learning parameters and anxiety level in comparison to control animals. Thus, the peptide the structure of which includes ACTH6-9 fragment and tripeptide PGP has nootropic and anxiolytic activity. Consequently, the spectrum of neurotropic activity of ACTH6-9PGP coincides with the spectrum of Semax activity, but the duration of its effects is much shorter.