Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice

作者：Rapacz Anna; Obniska Jolanta; Wiklik Poudel Beata; Rybka Sabina; Salat Kinga; Filipek Barbara

来源：European Journal of Pharmacology, 2016, 781: 239-249.

DOI：10.1016/j.ejphar.2016.04.033

• Anticonvulsant activity
• Formalin
• Oxaliplatin
• Motor coordination
• Ion channel binding
• Pyrrolidine-2
• 5-dione

The aim of the present experiments was to examine the anticonvulsant and antinociceptive activity of five new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in animal models of seizures and pain. The antiseizure activity was investigated in three acute models of seizures, namely, the maximal electroshock (MES), the subcutaneous pentylenetetrazole (scPTZ), and 6 Hz psychomotor seizure tests in mice. The antinociceptive properties were estimated in the formalin model of tonic pain, and in the oxaliplatin-induced neuropathic pain model in mice. Considering drug safety evaluation, acute neurological toxicity was determined in the rotarod test. Three tested compounds (3,4, and 7) displayed a broad spectrum of anticonvulsant activity and showed better protective indices than those obtained for MES/scPTZ/6 Hz active reference drug - valproic acid. Furthermore, three compounds (3, 4, and 6) demonstrated a significant antinociceptive effect in the formalin test, as well as antiallodynic activity in the oxaliplatin-induced neuropathic pain model. Among the tested agents, compounds 3 and 4 displayed not only antiseizure properties, but also collateral prominent analgesic properties. The in vitro binding study indicated that the plausible mechanism of action of chosen compound (4) was the influence on neuronal voltage-sensitive sodium (site 2) and L-type calcium channels.

• 出版日期2016-6-15