PMC

A1, Representative average mIPSC from a VB thalamic neuron before and after application of GHB. A2, GHB has no effect on the decay time constants of averaged mIPSCs in VB neurons. A3, Distribution of mIPSCs amplitude across 9 cells, showing no effect of GHB. B1, Representative average mIPSC from a dentate gyrus (DG) granule cell before and after application of GHB. B2, GHB has no effect on the decay time constants of averaged mIPSCs in dentate gyrus granule cells. B3, Distribution of mIPSCs amplitude across 6 cells, showing no effect of GHB. C1, Representative average mIPSC from a striatal medium spiny neuron (MSN) before and after application of GHB. C2, GHB has no effect on the decay time constants of averaged mIPSCs in medium spiny neurons. C3, Distribution of mIPSCs amplitude across 11 cells, showing no effect of GHB.

Possible pharmacological mechanisms of GHB. Structures of 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), two GHB prodrugs that are metabolized to GHB in vivo. Structures of GABA, GHB (sodium salt), and NCS-382. GABA and GHB are reversibly metabolized in vivo. Three possible pharmacological mechanisms for GHB. GHB is metabolized to GABA, which binds to GABA_A and GABA_B receptors, GHB binds to GABA_B and GHB receptors, and NCS-382 binds to GHB receptors. Selective ligands for GABA_A, GABA_B, and GHB receptors are shown below the respective depiction of each receptor.

GHB 600 mg/kg was administered intravenously daily for 5 days and GHB toxicokinetics measured on days 1 and 5, representing acute and chronic GHB administration, respectively.

Correlation between the GHB concentration and the GHB peak area integrated by XCMS: (A) correlation between GHB concentration and GHB peak area without log-transformation and data normalization. (B) correlation between GHB concentration and GHB peak area with log-transformation but without any data normalization, (C) correlation between GHB concentration and GHB peak area with log-transformation and NOMIS normalization. The peak area in y-axis is from screening method on UHPLC-QTOF, and concentration of x-axis is measured by UHPLC-QQQ. Only GHB positive samples were used in all the plots.