GABAB receptor antagonists: potential new anti-absence drugs.
The availability of new antagonists of the GABAB receptor which readily cross the blood-brain barrier has made it possible to investigate the role of GABAB-receptor-mediated transmission in the control of spike-and-wave discharges (SWD) in a strain of rats (GAERS) with genetic absence epilepsy. Systemic administration of R-Baclofen, a GABAB agonist, increased the duration of SWD, or elicited SWD-like oscillations in the cortical EEG of non-epileptic control rats. Conversely, administration of CGP 35348, a GABAB antagonist, either i.p. or p.o., dose-dependently suppressed the spontaneous SWD, as well as the SWD aggravated by concomitant injection of various GABAmimetic drugs, GHB, or anti-convulsants known to exacerbate absence seizures. These results demonstrate the involvement of GABAB-mediated neurotransmission in the development of SWD in generalized non-convulsive epilepsy. GABAB antagonists may thus be considered to be potentially specific anti-absence drugs.
Marescaux
C
C
Clinique Neurologique, C.H.U. Strasbourg, France.
Vergnes
M
M
Bernasconi
R
R
D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000502:physiology*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000503:physiopathology; D058787:GABA-A Receptor Antagonists; D007274:Injections, Intraperitoneal; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; C066430:CGP 35348; D001418:Baclofen