Anticonvulsant properties of N-(4-methylpiperazin-1-yl)- and N-[3-(4-methylpiperazin-1-yl)-propyl] derivatives of 3-aryl- and 3-spirocycloalkyl-pyrrolidine-2,5-dione

Abstract

Two series of N-(4-methylpiperazin-1-yl)- and N-[3-(4-methylpiperazin-1-yl)-propyl]-3-aryl- (3-10) and 3-spirocycloalkyl-pyrrolidine-2,5-dione (11-14) derivatives were synthesized and tested for anticonvulsant activity in the maximum electroshock (MES) seizure and pentetrazole (sc PTZ) seizure threshold tests. Compounds 3-10 with an aromatic ring at position-3 of pyrrolidine-2,5-dione exhibited anticonvulsant activity in the MES test. For that series of compounds, ED50 values were determined. The most potent in the series were derivatives 5, 6 and 9, 10 with a chlorine atom at position-3 or 4 of the aromatic ring. Those compounds exhibited strong anticonvulsant activity, and their ED50 values ranged from 29 to 48 mg/kg. Introduction of the spirocycloalkyl ring into the position-3 of pyrrolidine-2,5-dione (11-14) made those compounds inactive. Copyright © 2005 by Institute of Pharmacology Polish Academy of Sciences.