Evaluation of anticonvulsant activity of QUAN-0806 in various murine experimental seizure models.
A new quinoline derivative, QUAN-0806 (7-hexyloxy-5-phenyl-1,2,4-triazolo[4,3-alpha]quinoline) was tested for anticonvulsant activity using the maximal electroshock seizure (MES) and the rotarod neurotoxicity (Tox) tests in mice. The MES test showed that QUAN-0806 exhibited higher activity (ED50 = 6.5 mg/kg) and lower toxicity (TD50 = 228.2 mg/kg), resulting in a higher protective index (PI = 35.1) than the reference drugs phenytoin, carbamazepin, phenobarbital, and valproate. In addition, QUAN-0806 was found to exhibit significant oral activity against MES-induced seizures with low oral neurotoxicity in mice. QUAN-0806 was tested in chemically induced models (pentylenetetrazole, PTZ; isoniazid, ISO; 3-mercaptopropionic acid, 3-MPA; and strychnine, STRYC) to further investigate the anticonvulsant activity. QUAN-0806 produced significant antagonistic activity against seizures induced by PTZ, 3-MPA, and ISO, suggesting that QUAN-0806 influences GABAergic neurotransmission by activating glutamate decarboxylase (GAD) or inhibiting (GABA)-a-oxoglutarate aminotransferase (GABA-T) in the brain.
Guan
Li-Ping
LP
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Yanbian University, PR China.
Zhao
Dong-Hai
DH
Jiang
Zhe
Z
Piao
Hu-Ri
HR
Quan
Zhe-Shan
ZS
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003292:Convulsants / Q000494:pharmacology; D004597:Electroshock; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004856:Postural Balance / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
C540982:7-hexyloxy-5-phenyl-1,2,4-triazolo(4,3-alpha)quinoline; D000927:Anticonvulsants; D003292:Convulsants; D011804:Quinolines; D014230:Triazoles; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase