Levetiracetam opposes the action of GABAA antagonists in hypothalamic neurones.
Whole-cell current-clamp recordings in guinea-pig brain slices were used to assess the effect of the novel antiepileptic drug levetiracetam (LEV; Keppra) on the gamma-aminobutyric acid-A (GABA(A)) responses evoked by exogenous applications of the agonists GABA and muscimol on hypothalamic neurones. LEV (40 microM) had no direct effect on GABA(A) responses but it occluded the GABA(A)-receptor blocking action of bicuculline-methiodide (100 microM) and, to a lesser extent, the GABA(A)-receptor blocking action of gabazine (50 microM). While previous reports have indicated that the inhibition by LEV of the epileptiform hyperexcitability induced by bicuculline in rat hippocampus might occur via non-GABAergic mechanisms, the present data suggest a possible indirect modulation by LEV of GABA-gated currents in guinea-pig hypothalamic neurones.
Poulain
P
P
INSERM Unité 422, Place de Verdun, 59045 Lille Cedex, France. poulain@lille.inserm.fr
Margineanu
D G
DG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D000077287:Levetiracetam; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology
D000927:Anticonvulsants; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D000077287:Levetiracetam; D010889:Piracetam