Abstract |
The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.
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Authors | O Khongsombat, H Watanabe, B Tantisira, C Patarapanich, M H Tantisira |
Journal | Epilepsy research
(Epilepsy Res)
Vol. 79
Issue 2-3
Pg. 151-7
(May 2008)
ISSN: 0920-1211 [Print] Netherlands |
PMID | 18439803
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acids
- Anticonvulsants
- Muscarinic Agonists
- N-(2-propylpentanoyl)urea
- Neurotransmitter Agents
- Pilocarpine
- Valproic Acid
- Urea
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Topics |
- Amino Acids
(physiology)
- Animals
- Anticonvulsants
(pharmacology)
- Hippocampus
(drug effects, metabolism)
- Male
- Microdialysis
- Muscarinic Agonists
- Neurotransmitter Agents
(physiology)
- Pilocarpine
- Rats
- Rats, Wistar
- Seizures
(chemically induced, metabolism)
- Urea
(analogs & derivatives, pharmacology)
- Valproic Acid
(analogs & derivatives, pharmacology)
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