Analgesic activity of the low molecular weight neurotrophin-3 dipeptide mimetic GTS-301

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Abstract

It was previously shown that the original dipeptide mimetic of the 4th loop neurotrophin-3 (NT-3) hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), like full-size 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 after systemic administration on rodents – antidiabetic (0.1 and 0.5 mg/kg) and antidepressant (5 and 10 mg/kg) effects. 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% and the effect persisted for at least 24 hours after administration.

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About the authors

L. G. Kolik

FSBSI “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Author for correspondence.
Email: kolik_lg@academpharm.ru
Russian Federation, Moscow

M. A. Konstantinopolsky

FSBSI “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: kolik_lg@academpharm.ru
Russian Federation, Moscow

N. M. Sazonova

FSBSI “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: kolik_lg@academpharm.ru
Russian Federation, Moscow

A. D. Durnev

FSBSI “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: kolik_lg@academpharm.ru

Сorresponding Мember of the RAS

Russian Federation, Moscow

T. A. Gudasheva

FSBSI “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”

Email: kolik_lg@academpharm.ru

Сorresponding Мember of the RAS

Russian Federation, Moscow

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2. Fig. 1. Structure of the dimeric dipeptide mimetic NT-3 (compound GTS-301)

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3. Fig. 2. Effect of GTS-301 on the latency period of reaction in rats in the tail-flick test Note: *, ** – p<0.05, p<0.01 compared to the control group in the corresponding time period; the number of animals in each group was 8; data are presented as Mean±S.E.M.

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