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Antiabsence seizure activity of specific GABAB and gamma-Hydroxybutyric acid receptor antagonists.

Abstract
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.
AuthorsO C Snead 3rd
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 53 Issue 1 Pg. 73-9 (Jan 1996) ISSN: 0091-3057 [Print] United States
PMID8848463 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Anticonvulsants
  • Benzocycloheptenes
  • GABA Agonists
  • GABA Antagonists
  • GABA-B Receptor Antagonists
  • phaclofen
  • NCS 382
  • Baclofen
  • Pentylenetetrazole
  • 2-hydroxysaclofen
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Baclofen (analogs & derivatives, pharmacology)
  • Benzocycloheptenes (pharmacology)
  • Electroencephalography (drug effects)
  • Epilepsy, Absence (chemically induced, drug therapy)
  • GABA Agonists (pharmacology)
  • GABA Antagonists (pharmacology)
  • GABA-B Receptor Antagonists
  • Injections, Intraventricular
  • Isomerism
  • Male
  • Pentylenetetrazole
  • Rats
  • Rats, Sprague-Dawley

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