Analgetic activity of the newly synthesized compound from the class of Hexaazaisowurtzitanes: in vivo research in nociceptive tests

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Abstract
Objective. To assess analgesic action of the newly patented compound from the class of hexaazaisowurzitanes as compared to tramadol in a battery of behavioral tests with various nociceptive systems. Material and methods. The experiments were performed in male mice of CD1 stock. A newly patented 4-(2-ethoxyacetyl)-2.6,8.10.12-pentaacetyl2.4,6.8,10.12hexaazatetracyclo [5.5,0.03.11.05.9]dodecane (M1) was administered daily through a probe at a dose 25—200 mg/kg. Tramadol was administered in a single dose 10 mg /kg for 1-3 days. The last injection was an hour before experimental manipulations. Analgesic effect was evaluated in a three-day administration on a model of chemical irritation of the peritoneum, in a single administration (test of central pain genesis “hot plate”) and mechanical paw compression (Randall-Selitto method). Results. Analysis of specific pharmacological activity in models of somatogenic pain (thermal, visceral pain, mechanical compression) revealed high analgesic activity of the newly synthesized compound 4-(2-ethoxyacetyl)-2.6,8.10.12-pentaacetyl 2.4,6.8,10.12 hexaazatetracyclo[5.5,0.03.11.05.9]dodecane (substance M1). The last one is comparable or exceeds the effect of tramadol. Analgesic effect of the new compound is realized at different levels of conduction and modulation of pain sensitivity. Conclusion. The results of experimental tests with different nociception systems indicate advisability of further preclinical studies of the newly synthesized molecule with high analgesic therapeutic potential.

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