SEIZURES INDUCED BY AMINOOXYACETIC ACID in MICE - PHARMACOLOGICAL CHARACTERISTICS

SEIZURES INDUCED BY AMINOOXYACETIC ACID in MICE - PHARMACOLOGICAL CHARACTERISTICS

Author Turski, W. A. Google Scholar
Dziki, M. Google Scholar
Urbanska, E. Google Scholar
Calderazzofilho, L. S. Google Scholar
Cavalheiro, E. A. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04-mu-mol (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97; 150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L-Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. the seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1-mu-mol) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D-glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid.The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug.
Keywords ANTIEPILEPTIC DRUGS
AMINOOXYACETIC ACID
EPILEPSY
EXCITATORY AMINO ACID ANTAGONISTS
Language English
Date 1991-03-01
Published in Synapse. New York: Wiley-liss, v. 7, n. 3, p. 173-180, 1991.
ISSN 0887-4476 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 173-180
Origin http://dx.doi.org/10.1002/syn.890070302
Access rights Closed access
Type Article
Web of Science ID WOS:A1991FA35500001
URI http://repositorio.unifesp.br/handle/11600/25192

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