Analgesic Activity of the Low Molecular Weight Neurotrophin-3 Dipeptide Mimetic GTS-301.

Abstract

It was previously shown that the original dipeptide mimetic of the 4th loop of neurotrophin-3 (NT-3) hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), like the full-length neurotrophin, predominantly activates the tyrosine kinase receptor TrkC and has a neuroprotective effect in vitro at concentrations of 10^-5-10^-12 M, as well as antidiabetic (0.1 and 0.5 mg/kg) and antidepressant (5 and 10 mg/kg) effects after systemic administration in rodents. In this work, the analgesic properties of GTS-301 were identified, which were manifested in the dose range of 0.01-10 mg/kg after acute intraperitoneal injection to rats in the "tail flick" test. Dipeptide GTS-301 increased the threshold of pain response by 20-30%; this effect persisted for at least 24 h after administration.