The aim of the present experiments was to examine
anticonvulsant activity of new
pyrrolidine-2,5-dione and 3-methylpyrrolidine-2,5-dione derivatives in animal models of
epilepsy. In addition, the possible collateral antinociceptive activity was assessed.
Anticonvulsant activity was investigated in the electroconvulsive threshold (MEST) test and the
pilocarpine-induced seizure models in mice. Antinociceptive activity was examined in the hot plate and the
formalin tests in mice. Considering the
drug safety evaluation, the Vibrio harveyi test was used to estimate anti/mutagenic activity. To determine the plausible mechanism of
anticonvulsant action, for two chosen compounds (12 and 23), in vitro binding assays were carried out. All of the tested compounds revealed significant
anticonvulsant activity in the MEST test. Compounds 12 and 23 displayed
anticonvulsant effect also in
pilocarpine-induced
seizures. Four of the tested compounds (12, 13, 15, and 24) revealed
analgesic activity in the hot plate test as well as in the first phase of the
formalin test, and all of them were active in the second phase of the
formalin test. The possible mechanism of action of compounds 12 and 23 is the influence on the neuronal voltage-sensitive
sodium and
L-type calcium channels. The obtained results indicate that in the group of pyrrolidine-2,5-diones, new
anticonvulsants with collateral
analgesic properties can be found.