Seizures induced by aminooxyacetic acid in mice: pharmacological characteristics.
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 mumols (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 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-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.
Turski
W A
WA
Department of Pharmacology, Medical School, Lublin, Poland.
Dziki
M
M
Urbanska
E
E
Calderazzo-Filho
L S
LS
Cavalheiro
E A
EA
D000625:Aminooxyacetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D003975:Diazepam / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D000927:Anticonvulsants; D000625:Aminooxyacetic Acid; D003975:Diazepam; D010634:Phenobarbital