Abstract
BackgroundEpilepsy is the most prevalent neurological disorder, affecting approximately 50 million people worldwide. Even though significant advances have been made in epilepsy research, convulsions in about 30% of epileptics are still inadequately controlled by standard drug therapy. For this reason, constant attempts are made to investigate new chemical agents and mechanisms through which epilepsy can be effectively controlled. Therefore, in the present studies, a series of sixteen new 1-[(4-arylpiperazin-1-yl)-propyl]-3-methyl-3-phenyl- and 3-ethyl-3-methylpyrrolidine-2,5-dione derivatives as potential anticonvulsant agents was synthesized. MethodsAnticonvulsant properties were evaluated in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and psychomotor seizure (6-Hz) tests after intraperitoneal injection in mice. The acute neurological toxicity was determined in the motor impairment rotorod screen. ResultsThe compounds showed activity at a dose of 30mg/kg (4, 8, 16) or 100mg/kg (6, 9, 10, 12, 17, 18) in the MES model in mice. Four or them (8, 10, 16, 17) were also evaluated after po administration in rats. In this series, the most active was 1-{3-[4-(3-chlorophenyl)-piperazin-1-yl]-propyl}-3-methyl-3-phenyl-pyrrolidine-2,5-dione (8) with the ED50 value of 28.2mg/kg, TD50 value of 268.5mg/kg and protective index of 9.52 after po administration in rats. ConclusionsTaking into consideration the role of 5-HT1A and 5-HT7 receptor subtypes in relation to the control of seizures as well as the fact that all compounds obtained belong to the class of long-chain arylpiperazines, their serotonin 5-HT1A and 5-HT7 receptor affinity was determined. The most potent 5-HT1A receptor ligands are 2-OCH3 (11, 19) and 3-Cl (8, 16) derivatives with Ki = 72, 14nM, and 109, 44nM, respectively. With respect to the 5-HT7 receptors, the best Ki values were obtained for derivatives 8 and 11 (Ki = 76nM and 63 nM, respectively).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.