Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 19, Issue 20, Pages 6149-6156Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.08.017
Keywords
N-Mannich bases; 5-Cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-dione; Hydantoin; Anticonvulsant activity
Funding
- Minister Committee for Scientific Research, Poland [N405 298536]
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Synthesis, physicochemical and anticonvulsant properties of new N-Mannich bases derived from 5-cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-diones have been described. Initial anticonvulsant screening was performed using intraperitoneal (ip.) maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The neurotoxicity was determined applying the rotarod test. The in vivo results in mice showed that all compounds were effective especially in the MES screen. The quantitative evaluation after oral administration in rats showed that the most active was 5-cyclopropyl-5-phenyl-imidazolidine-2,4-dione (1) with ED50 values of 5.76 mg/kg (MES) and 57.31 mg/kg (scPTZ). This molecule was more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. Additionally compound 1 with ED50 of 26.06 mg/kg in psychomotor seizure test (6-Hz) in mice showed comparable activity to new generation anticonvulsant - levetiracetam. (C) 2011 Published by Elsevier Ltd.
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