Substituted Glyproline GZK-111 Retains Antihypoxic and Anxiolytic Activity Upon Peroral Administration

Recently, the substituted dipeptide N-phenylacetylglycyl-L-proline ethyl ester (GZK-111), which is metabolized in vivo to cycloprolylglycine (CPG), which is identical to an endogenous cycloneuropeptide, was designed and synthesized at V. V. Zakusov Institute of Pharmacology. GZK-111 possessed all activities characteristic of CPG (nootropic, anxiolytic, antihypoxic, neuroprotective, and analgesic) after intraperitoneal administration to rodents at doses ranging from 0.1 to 5 mg/kg. The present work showed that GZK-111 also preserved its pharmacological effects after peroral administration. GZK-111 after peroral administration exhibited antihypoxic activity at doses of 10 and 30 mg/kg in mice in a hypoxia with hypercapnia model. The anxiolytic activity of GZK-111 was retained after peroral administration at a dose of 40 mg/kg in rats in the elevated plus-maze test. Preservation of the pharmacological effects of substituted dipeptide GZK-111 after peroral administration is important for its development as a new potential drug for treatment of chronic diseases.

Automated summary

The substituted dipeptide GZK-111 retains its pharmacological effects, including antihypoxic and anxiolytic activities, after oral administration, which is important for its development as a potential drug for treating chronic diseases.