Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Anticonvulsant Activity and 5-HT1A/5-HT7 Receptors Affinity of Piperazine Derivatives of 3,3-Diphenyl- and 3,3-Dimethyl-succinimides

Author(s): Jolanta Obniska, Iwona Chlebek, Krzysztof Kaminski, Andrzej J. Bojarski, Grzegorz Satala.

Abstract:

The series of thirty new 1-[(4-arylpiperazin-1-yl)-alkyl]-3,3-diphenyl- and 3,3-dimethyl-pyrrolidine-2,5-diones was synthesized. The anticonvulsant properties were evaluated in maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests after intraperitoneal injection in mice. The motor impairment was determined in the rotorod test in parallel. Although no anti-seizure properties were found in the scPTZ screen, fourteen compounds showed protection in the MES test at a dose of 100 mg/kg which is known as animal model of human generalized tonicclonic seizures. Taking into consideration the role of 5-HT1A and 5-HT7 receptor subtypes in seizures control as well as the fact that all compounds obtained belong to the class of long-chain arylpiperazines (LCAPs), their 5-HT1A and 5-HT7 serotonin receptor affinities were determined. The most potent 5-HT1A receptor ligands are 2-OCH3 (20, 35), 3-Cl (32) and 3-CF3 (34) derivatives with Ki = 16 nM (20), 33 nM (35), 32 nM (32) and 26 nM (34). Compounds 32 and 35 reveled also high 5-HT7 receptors affinity with the the Ki values 70 nM and 47 nM, respectively. There was no correlation between anticonvulsant properties and 5-HT1A and/or 5-HT7 serotonin receptor affinity.

Keywords: Anticonvulsant activity; 5-HT1A/5-HT7 receptor ligands; Arylpiperazines; 3, 3-Disubstituted pyrrolidine-2, 5-diones; In vivo studies; In vitro studies; Succinimides.

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2013
Page: [173 - 182]
Pages: 10
DOI: 10.2174/157018013804725116
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