Abstract | PURPOSE: METHODS: VGD was administered intraperitoneally to CF no. 1 mice and orally or intraperitoneally to Sprague-Dawley rats. The anticonvulsant activity of VGD was examined in nine different animal models of epilepsy for its ability to block electrically, chemically, or sensorily induced seizures. RESULTS: In mice VGD afforded complete protection against maximal electroshock (MES)-, pentylenetetrazole-, picrotoxin-, and bicuculline-induced seizures and 6-Hz "psychomotor" seizures with median effective dose (ED50) values of 151, 132, 275, 248, and 237 mg/kg, respectively. VGD was also effective in preventing sound-induced seizures in Frings audiogenic-seizure susceptible mice (ED50, 52 mg/kg). The median neurotoxic dose in mice was 332 mg/kg. After oral administration to rats, VGD was active in the MES test, with an ED50 of 73 mg/kg, and the median neurotoxic dose was 1,000 mg/kg. Intraperitoneal administration of 300 mg/kg of VGD to hippocampal kindled Sprague-Dawley rats blocked generalized seizures and shortened the afterdischarge duration significantly. VGD also provided complete protection from focal seizures in the corneally kindled rats (ED50,161 mg/kg). CONCLUSIONS: The results obtained in this study suggest that VGD has a broad spectrum of anticonvulsant activity and promising potential as a new AED.
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Authors | N Isoherranen, J H Woodhead, H S White, M Bialer |
Journal | Epilepsia
(Epilepsia)
Vol. 42
Issue 7
Pg. 831-6
(Jul 2001)
ISSN: 0013-9580 [Print] United States |
PMID | 11488880
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anticonvulsants
- TV 1901
- Glycine
- Pentylenetetrazole
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Topics |
- Acoustic Stimulation
- Animals
- Anticonvulsants
(pharmacology)
- Behavior, Animal
(drug effects)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Electroshock
- Epilepsy
(chemically induced, etiology, prevention & control)
- Epilepsy, Reflex
(prevention & control)
- Glycine
(analogs & derivatives, pharmacology)
- Hippocampus
(drug effects, physiology)
- Kindling, Neurologic
(drug effects)
- Male
- Mice
- Motor Activity
(drug effects)
- Pentylenetetrazole
- Rats
- Rats, Sprague-Dawley
- Seizures
(chemically induced, etiology, prevention & control)
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