ANTICONVULSANT POTENCY OF 10 VARIOUS P-ISOPROPOXYPHENYLSUCCINIMIDE DERIVATIVES IN THE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE THRESHOLD MODEL IN MICE

Background. To compare the anticonvulsant potency of 10 various p-isopropoxyphenylsuccinimide (IPPS) derivatives [i.e., IPPS (IPPS); N-(morpholinomethyl)- IPPS (MM-IPPS); N-(anilinomethyl)-IPPS (AM-IPPS); N-hydroxymethyl-IPPS (HM-IPPS); N-(p-acetylphenyl)-IPPS (AP-IPPS); N-(p-ethoxycarbonylphenylmethyl)-IPPS (ECPM-IPPS); N-(m-bromoanilinomethyl)-IPPS (BAM-IPPS); N-(o-carboxyanilinomethyl)-IPPS (o-CAM-IPPS); N-(m-carboxyanilinomethyl)-IPPS (m-CAM-IPPS); N-(p-carboxyanilinomethyl)-IPPS (p-CAM-IPPS)] in the maximal electroshock-induced seizure threshold (MEST) test in mice. Material and methods. Linear regression analysis of doses of IPPS derivatives and their threshold increases in the MEST test in mice allowed to calculate TID20 values i.e., doses of the tested IPPS derivatives that elevate by 20% the seizure threshold in IPPS-treated mice over the threshold in control animals. Results. A ll t he studied IPPS derivatives (i.e., IPPS, MM-IPPS, HM-IPPS, AP-IPPS, AM-IPPS, ECPM-IPPS, o-CAM-IPPS, m-CAM-IPPS, p-CAM-IPPS and BAM-IPPS) increased in a dose dependent manner the threshold for maximal electroshock-induced seizures in mice. The TID20 values in the MEST test for IPPS, AP-IPPS, AM-IPPS, BAM-IPPS, o-CAM-IPPS, m-CAM-IPPS, p-CAM-IPPS, ECPM-IPPS, HM-IPPS, and MM-IPPS were 60.44 mg/kg, 86.30 mg/kg, 44.69 mg/kg, 103.34 mg/kg, 22.43 mg/kg, 52.84 mg/kg, 80.85 mg/kg, 109.75 mg/kg, 32.62 mg/kg and 53.50 mg/kg, respectively. Conclusions. The studied IPPS derivatives with respect to their anticonvulsant potency in the MEST test can be arranged as follows: o-CAM-IPPS > HM-IPPS > AM-IPPS > m-CAM-IPPS > MM-IPPS > IPPS > p-CAM-IPPS > AP-IPPS > BAM-IPPS > ECPM-IPPS.