Abstract |
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.
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Authors | Li-Ping Guan, Dong-Hai Zhao, Zhe Jiang, Hu-Ri Piao, Zhe-Shan Quan |
Journal | Die Pharmazie
(Pharmazie)
Vol. 64
Issue 4
Pg. 248-51
(Apr 2009)
ISSN: 0031-7144 [Print] Germany |
PMID | 19435143
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 7-hexyloxy-5-phenyl-1,2,4-triazolo(4,3-alpha)quinoline
- Anticonvulsants
- Convulsants
- Quinolines
- Triazoles
- gamma-Aminobutyric Acid
- 4-Aminobutyrate Transaminase
- Glutamate Decarboxylase
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Topics |
- 4-Aminobutyrate Transaminase
(metabolism)
- Animals
- Anticonvulsants
(pharmacokinetics, pharmacology)
- Brain
(drug effects, enzymology)
- Convulsants
(pharmacology)
- Electroshock
- Enzyme Activation
(drug effects)
- Female
- Glutamate Decarboxylase
(metabolism)
- Injections, Intraperitoneal
- Male
- Mice
- Mice, Inbred C57BL
- Postural Balance
(drug effects)
- Quinolines
(pharmacology)
- Seizures
(chemically induced, prevention & control)
- Synaptic Transmission
(drug effects)
- Triazoles
(pharmacology)
- gamma-Aminobutyric Acid
(physiology)
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