Antinociceptive properties of N-Mannich bases derived from 3-substituted pyrrolidine-2,5-dione in the formalin model of persistent pain in mice

Background: Accumulated data indicate that anticonvulsants possess antinociceptive properties in rodent pain models. In view of the anticonvulsant activity demonstrated previously among N-Mannich bases derived from 3-mono- (1-6) and 3,3-disubstituted pyrrolidine-2,5-diones (7-14) their analgesic activity has been investigated in the formalin model of tonic pain in mice. Methods: The compounds 1-14 were tested at doses equal to the respective ED50 values obtained earlier in the MES test. 0.5% formalin solution was given as intraplantar injections into the hind paw of the mouse and the duration of the nocifensive response was counted in drug-treated and vehicle-treated animals in the acute and the late phases of the test. Results: A significant antinociceptive activity was observed for majority of the compounds. In the first phase of the test all the active compounds, except for 9-11, reduced the duration of the licking response up to 88% (compounds 2 and 6; p < 0.001). In the late phase the 1-3,5,6,9 and 14 were the most effective agents and their analgesic activities ranged from 92 to 100%. Conclusions: The results of the research indicate that some of the investigated compounds reduced effectively either both phases of the test or were able to attenuate pain during only the acute or late phase of the formalin test. These properties, which are particularly strong in case of the compounds 1-3, 5,6,9 and 14, might be relevant for the development of novel analgesic-active compounds and their possible use in neuropathic pain syndromes. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.