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