Investigation of imidazole-4,5-dicarboxylic acid derivatives activity on visceral pain in mice

Introduction: Glutamate plays an important role in the modulation of nociception. Experimental studies on rodents have shown that mGluR1 receptor inhibitors demonstrate antinociceptive potential in acute pain models. New ligands of the glutamate NMDA-receptor complex are imidazole-4,5-dicarboxylic acid derivatives, which conformational rigidity allows increasing selectivity interaction and decreasing a number of side effects with the implementiation a high analgesic potential. Materials and Methods: Intraperitoneal administration of algogen – 1.5% acetic acid solution –causes chemical pain irritation, manifested by specific animal movements called writhing. Fifteen minutes before the administration of 1.5% acetic acid solution, mice were intraperitoneally administered the experimental substances: IEM-303 at a dose of 50 mg/kg and IEM-2347 at doses of 10, 20, and 40 mg/kg. The control group of animals received a physiological solution in an equivalent volume, and the comparison group received metamizole sodium at a dose of 100 mg/kg. The analgesic effect was assessed by the ability of the drugs to reduce the number of writhings in comparison with the control group. Results: The introduction of substance IEM-2347 at a concentration of 10 mg/kg led to a decrease in the number of writhings to 6.3 ± 3.1 units (by 89.4%), which significantly exceeds the indicators obtained in the group receiving metamizole sodium. With a further increase in IEM-2347 concentration to 20-40 mg/kg, complete suppression of the pain response was observed in 100% of animals. Discussion: It can be assumed that the elongation of radicals in the benzene ring at nitrogen atoms has an effect enhancing the analgesic potential of the imidazole dicarboxylic acid derivative. Conclusion: High analgesic potential with toxicological safety of imidazole-4,5-dicarboxylic acid derivatives allows them to be considered as promising pain relievers.