Antiabsence seizure activity of specific GABAB and gamma-Hydroxybutyric acid receptor antagonists.
Hydroxybutyric acid (GHB) is a naturally occurring compound that has the ability to induce generalized absence seizures possibly by GABAB-receptor-mediated mechanisms. The object of these experiments was to examine the effectiveness of a range of specific GABAB-receptor agonists and antagonists of varying specificity, as well as the specific GHB-receptor antagonist NCS 382, in two experimental animal models of generalized absence seizures: one in which the seizures are induced by GHB and the other in which the seizures are induced by administration of low-dose (20-mg/kg) pentylenetetrazole. All specific GABAB-receptor antagonists as well as the specific GHB-receptor antagonist produced blockade of experimental absence seizures in both models; pretreatment with GABAB-receptor agonists resulted in generalized absence status epilepticus lasting for hours. These data confirm the concept that specific GABAB-receptor antagonist activity confers antiabsence seizure activity, suggest that the same holds for specific GHB-receptor antagonists, and raise the possibility that both GHB- and GABAB-antagonist drugs have the potential to be useful therapeutic agents in generalized absence seizures.
Snead
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OC
Department of Neurology, Childrens Hospital Los Angeles, University of Southern California, School of Medicine, Los Angeles, USA.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001567:Benzocycloheptenes / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D007276:Injections, Intraventricular; D007536:Isomerism; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D001567:Benzocycloheptenes; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; C052329:phaclofen; C066471:NCS 382; D001418:Baclofen; D010433:Pentylenetetrazole; C057491:2-hydroxysaclofen