Study of acute toxicity of dimeric dipeptide mimetic of neurotrophin-3 in mice

Abstract

Introduction. Low-molecular-weight mimetics of neurotrophin-3 (NT-3) are considered promising compounds for the development of novel drugs. One of the first stages in the preclinical studies of candidate drugs is the assessment of acute toxicity. The aim of this work was to evaluate the acute toxicity of the novel dimeric dipeptide mimic of the fourth loop of NT-3 (compound GTS-301) after intraperitoneal administration in female and male outbred mice.Materials and methods. GTS-301 (hexamethylenediamide bis-(N-monosucciny L-asparaginy L-asparagine), substance in 1 % starch solution) was administered acutely intraperitoneally to mice in the maximum possible volume and concentration. The control group received an equivalent volume of 1 % starch solution. The time course of intoxication development in mice was recorded, along with a detailed description of the observed clinical signs. Euthanasia and postmortem examination were performed on the 15th day after GTS-301 administration.Results. During a 14-day observation of mice that received GTS-301 at doses of 1 and 2 g/kg, caused the death of only one animal after the administration of the GTS-301 to the maximum permissible volume and the maximum possible concentration (2 g/kg) that did not allow calculating the median lethal dose of the compounds for mice. The morphological examination of internal organs during postmortem dissection of all experimental animals did not differ from that observed in controls.Conclusion. It was determined that dipeptide mimetic of neurotrophin-3 (GTS-301) after acute intraperitoneal administration concerns to be practically non-toxic substance. According to classification by Sidorov K.K. (1973), this compound may be related to 5th toxicity class.

Keywords

• neurotrophin-3
• gts-301
• acute toxicity
• mice