Synthesis and Investigation of the Antidepressant Properties of Novel Analogs of Arginine-Vasopressin

A search for novel antidepressant analogs of arginine-vasopressin (AVP) by a computer modeling revealed the following peptide analogs of the C-terminal part of AVP: N-Ac-D-Ser-Pro-D-Arg-Gly-NH2, N-Ac-Phe-Pro-Arg-Gly-NH2, and N-Ac-Trp-Pro-Arg-Gly-NH2. Syntheses of the modeled compounds were described in this article. The compounds that could potentially exhibit the antidepressant activity were examined in the forced swimming test. N-Ac-Trp-Pro-Arg-Gly-NH2 (0.1, 1.0, and 10.0 mu g/kg) and N-Ac-D-Ser-Pro-D-Arg-Gly-NH2 (1.0 mu g/kg) were shown to have the highest similarity to the fluoxetine reference antidepressant according to a number of parameters after the intranasal administration to the Wistar male rats.