PT - JOURNAL ARTICLE AU - Viviane Hechler AU - Charline Ratomponirina AU - Michel Maitre TI - γ-Hydroxybutyrate Conversion into GABA Induces Displacement of GABA<sub>B</sub> Binding that is Blocked by Valproate and Ethosuximide DP - 1997 May 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 753--760 VI - 281 IP - 2 4099 - http://jpet.aspetjournals.org/content/281/2/753.short 4100 - http://jpet.aspetjournals.org/content/281/2/753.full SO - J Pharmacol Exp Ther1997 May 01; 281 AB - γ-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB receptor(s), although with low or very low affinity (IC50 = 150–796 μM). In addition, several reports argue for a role of GHB via GABAB receptors in bothin vivo and in vitro electrophysiological experiments. In the present study, we demonstrate that the inhibition of GHB’s conversion into GABA by rat brain membranes blocks the ability of GHB to interfere with GABAB binding. In particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding could explain the misinterpretation of in vit́ro or in vivo experiments where GHB possesses a GABA-like effect. But in addition, it is postulated that the normal metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the administration of valproate or ethosuximide. The American Society for Pharmacology and Experimental Therapeutics