Synthesis and Antinociceptive Activity of GABA and Pyroglutamic Acid Short Peptides

The antinociceptive activity of new synthesized short peptides of γ-aminobutyric acid (GABA) with pyroglutamate (pGlu) – pyroglutamyl GABA (pGlu-GABA), pyroglutamyl GABA ethyl ester (pGlu-GABA ethyl ester), and pyroglutamyl diGABA (pGlu-GABA-GABA) – has been investigated. The peptides were administered to rats in a dose of 20 mg/kg separately and in combination with pregabalin, in the same dose. Results of the tail flick test demonstrated that intraperitoneal administration of all the investigated substances exhibited antinociceptive activity, leading to increase in the tail flick latency time. The maximum value of the tail flick latency for all peptides was manifested after 90 min of administration and was higher compared to the same characteristics in the control group as follows: for pGlu-GABA, 20.5%; for pGlu-GABA ethyl ester, 40.99%; and for pGlu-diGABA, 33,23%. In addition to the own antinociceptive activity of investigated peptides, the ability to potentiate the analgesic efficacy of pregabalin was revealed.