Study of anxiolytic activity and possible side effects of the dipeptide ligand of the translocator protein TSPO — compound GD-102 in a wide range of doses in behavioral experiments using rats and mice

Background . The dipeptide TSPO ligand, the compound amide N-phenylpropionyl-L-tryptophanyl-L-leucine (GD-102) was designed and synthesized in the Federal research center for innovator and emerging biomedical and pharmaceutical technologies. It was shown that GD-102 possessed anxiolytic and antidepressant-like activity in behavioral experiments using mice. The aim of this work was studying the anxiolytic activity and possible side effects of GD-102 in a wide range of doses from 0.01 to 5.0 mg/kg in experiments using rats and mice. Materials and methods . The pharmacological effects of GD-102 were studied with single intraperitoneal administration. The anxiolytic activity of GD-102 was studied in rats in the elevated plus maze test. The "climbing on the net" test was used to record orientation-exploratory behavior; the muscle relaxant properties were studied in the "rotating rod" and "horizontal bar" tests. Results . It was found that GD-102 at doses of 1.0 and 0.1 mg/kg (once administration), has a pronounced anxiolytic effect in the elevated plus maze test, significantly increasing the time the rats spent in the open arms of the maze and the number of entries into the open arms of the maze. The study of the sedative/activating effects on various behavior models indicated that GD-102 in a wide range of doses (from 0.01 to 5.0 mg/kg) did not affect orientation-exploratory behavior. In the dose range from 0.01 to 5.0 mg/kg, compound GD-102 does not impair the coordination of movements in the rotating rod test and the pull-up reflex on a horizontal bar, which indicates that compound GD-102 have not side effect on muscle relaxantion. Conclusion . The obtained results allow us to conclude that the dipeptide ligand of the TSPO translocator protein, compound GD-102, has a pronounced anxiolytic effect and does not have a sedative or muscle relaxant effect in a wide range of doses, which determines the feasibility of its further expanded preclinical study.