INVESTIGATION OF THE ANALGESIC ACTIVITY OF NEW LIGANDS OF THE NMDA RECEPTOR COMPLEX

Abstract

According to the Russian Society for the Study of Pain, 90% of patients seeking medical help experience pain, with 70% suffering from chronic pain [15, 16]. It should be acknowledged that the capabilities of traditional analgesic methods are limited, and the prescription of opioids is associated with an increase in complications, the development of tolerance, drug dependence, and an increase in the patient's hospital stay costs. Thus, the main directions for improving pain relief include the rational combination of analgesics with different mechanisms of action and the development of new effective and safe medicinal substances with analgesic activity. It is known that the activation of spinal cord NMDA receptors is a key factor in the pathogenesis of acute and chronic pain. Therefore, the use of existing NMDA antagonists in analgesic schemes, as well as the development of new compounds targeting the NMDA receptor complex, is of particular interest. New ligands of the glutamate NMDA receptor complex are derivatives of imidazole-4,5-dicarboxylic acid. The conformational rigidity of the molecules of imidazole-4,5-dicarboxylic acid derivatives allow for increased selectivity of interaction and reduced side effects. The aim of the study was to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex - derivatives of imidazole-4,5-dicarboxylic acid in mice using the tail-flick test and the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, 20 mg/kg. Мetamizole was used as a comparison drug. The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds in experimental models of acute pain at doses of 5-20 mg/kg. In the groups receiving IEM-2044 and IEM-303, the tail-flick latency increased by 1.4-1.7 times compared to the control group. The analgesic activity of the tested compounds at doses of 10-20 mg/kg was comparable to the analgesic activity of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics among this pharmacological class.