title: Synthesis and anticonvulsant activity evaluation of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinoline derivatives.
abstract: Two series of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinolines and 8-alkoxy-5-(2H-1,2,4-triazol-3-one-4-yl)quinolines were synthesized. The anticonvulsant activity of these compounds was evaluated with maximal electroshock seizure test and rotarod test. Among the synthesized compounds, 8-octoxy-5-(4H-1,2,4-triazol-4-yl)quinoline (4g) was the most active compound with ED(50) of 8.80 mg/kg, TD(50) of 176.03 mg/kg and protective index of 20.0. Its neurotoxicity was lower than all other synthesized compounds and also markedly lower than that of the reference drug carbamazepine. In addition, the potency of compound 4g 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, No. 977 Park Road, Yanji 133002, Jilin, China.
authors: Shi-Ben
authors: SB
authors: Wang
authors: Xian-Qing
authors: XQ
authors: Deng
authors: Yan
authors: Y
authors: Zheng
authors: Hong-Jian
authors: HJ
authors: Zhang
authors: Zhe-Shan
authors: ZS
authors: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D011804:Quinolines