title: Design, synthesis and anticonvulsant activity evaluation of novel 4-(4-substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones.
abstract: A series of novel 4-(4-substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-one derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock test (MES) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (TOX). In the MES test, compound 4-{4-[(3-fluorobenzyl)oxy]phenyl}-3-methyl-1H-1,2,4-triazol-5(4H)-one (4n) was found to possess better anticonvulsant activity and higher safety than marketed drugs Carbamazepine with an ED50 value of 25.5 mg/kg and protective index (PI) value>48.8. In addition, the potency of compound 4n against seizures induced by Pentylenetetrazole, 3-Mercaptopropionic acid, and Bicuculline suggested its broad spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might involve in its anticonvulsant activity.
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: Y
authors: Y
authors: Zheng
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: S-B
authors: SB
authors: Wang
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: X
authors: X
authors: Cao
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: D-C
authors: DC
authors: Liu
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: B
authors: B
authors: Shu
authors: College of Pharmacy, Yanbian University, Jilin, China.
authors: Z-S
authors: ZS
authors: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D002220:Carbamazepine; D003292:Convulsants; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D007202:Indicators and Reagents; D014230:Triazoles; D002220:Carbamazepine; D010433:Pentylenetetrazole