title: Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.
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.
authors.affiliation: Inter-department of Physiology, Graduate School, Chulalongkorn University, Bangkok 10330 Thailand.
authors.forename: O
authors.initials: O
authors.lastname: Khongsombat
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: B
authors.initials: B
authors.lastname: Tantisira
authors.forename: C
authors.initials: C
authors.lastname: Patarapanich
authors.forename: M H
authors.initials: MH
authors.lastname: Tantisira
mesh_terms: D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents / Q000502:physiology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D018721:Muscarinic Agonists; C108761:N-(2-propylpentanoyl)urea; D018377:Neurotransmitter Agents; D010862:Pilocarpine; D014635:Valproic Acid; D014508:Urea