Continuous sedation during spinal anaesthesia: gamma-hydroxybutyrate vs. propofol

Kleinschmidt, S.; Schellhase, C.; Mertzlufft, F.

doi:10.1046/j.1365-2346.1999.00393.x

Cited by 30 publications

(20 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been used clinically as an anesthetic (4) and in the treatment of sleep disorders (5). It has also gained notoriety as a recreational drug and as a drug used by sexual predators in date rape cases (6).…”

Section: ␥-Hydroxybutyrate (Ghb)mentioning

confidence: 99%

Synthesis and Catabolism of γ-Hydroxybutyrate in SH-SY5Y Human Neuroblastoma Cells

Lyon¹,

Johnston

Watson

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

␥-Hydroxybutyrate (GHB) is an endogenous metabolite synthesized in the brain. There is strong evidence to suggest that GHB has an important role as a neurotransmitter or neuromodulator. The human aldo-keto reductase AKR7A2 has been proposed previously to catalyze the NADPH-dependent reduction of succinic semialdehyde (SSA) to GHB in human brain. In this study we have used RNA interference to evaluate the role of AKR7A2 in GHB biosynthesis in human neuroblastoma SH-SY5Y cells. Quantitative reverse transcription-PCR analysis and immunoblotting revealed that short interfering RNA molecules directed against AKR7A2 led to a significant reduction in both AKR7A2 transcript and protein levels 72 h post-transfection. We have shown that reduced expression of AKR7A2 results in a 90% decrease in SSA reductase activity of cell extracts. Furthermore, we have shown using gas chromatography-mass spectrometry that a decrease in the level of AKR7A2 was paralleled with a significant reduction in intracellular GHB concentration. This provides conclusive evidence that AKR7A2 is the major SSA reductase in these cells. In contrast, short interfering RNA-dependent reduction in AKR7A2 levels had no effect on the GHB dehydrogenase activity of the extracts, and inhibitor studies suggest that another enzyme characteristic of an NAD-dependent alcohol dehydrogenase may be responsible for catalyzing this reverse reaction. Together these findings delineate pathways for GHB metabolism in the brain and will enable a better understanding of the relationship between GHB biosynthesis and catabolism in disease states and in drug overdose.

show abstract

Section: ␥-Hydroxybutyrate (Ghb)mentioning

confidence: 99%

Synthesis and Catabolism of γ-Hydroxybutyrate in SH-SY5Y Human Neuroblastoma Cells

Lyon¹,

Johnston

Watson

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…sie verdrängt worden war, wird GHB zurzeit wieder in zunehmendem Maße als Sedierungskomponente bei der Analgosedierung von Intensivpatienten, bei der Therapie des Alkohol-und auch des Opiat-Entzugssyndroms [2][3][4][5][6][7][8][9][10], der Narkolepsie [11][12][13] sowie zur Sedierung von Kindern für MRT-Untersuchungen eingesetzt [14][15].…”

unclassified

Gamma-hydroxy butyric acid: Neurotransmitter, sedative and party drug

Meyer

Kleinschmidt

Gottschling

et al. 2005

Wien Med Wochenschr

View full text Add to dashboard Cite

Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was first introduced in clinical anaesthesic practice more than 40 years ago. The drug was nearly forced from clinical practice because of its prolonged and variable duration of action. The results of recent clinical studies indicate a re-evaluation of GHB in various clinical fields. In the intensive care unit, GHB may be a favourable alternative to established drugs. The results of various clinical studies also suggest that GHB is efficacious in the treatment of alcohol withdrawal syndrome, and narcolepsy. GHB has been used successfully for short-term sedation in children. In addition, GHB has emerged as a street drug ("liquid ecstasy"). Overdose may lead to respiratory depression, coma, and even death. Chronic abuse itself may lead to severe withdrawal syndrome. The purpose of this article is to outline the neurophysiological, pharmacodynamic and pharmacokinetic characteristics of GHB, and to summarize the potential fields of use and misuse of GHB in clinical medicine and toxicology.

show abstract

“…Peripherally administered GHB can readily cross the blood-brain barrier and produces significant behavioral, electrophysiological, and biochemical effects. Clinically, GHB has been used as an anesthetic agent (2), in the treatment of alcohol withdrawal and dependence (3), opiate withdrawal (4), and in sleep disorders (5). Recently GHB has emerged as a major recreational drug of abuse, and its abuse or intoxication has been associated with a mild euphoria, respiratory depression, headache, vomiting, agitation, seizures, and even death (6 -8).…”

mentioning

confidence: 99%

γ-Hydroxybutyrate Reduces Mitogen-activated Protein Kinase Phosphorylation via GABAB Receptor Activation in Mouse Frontal Cortex and Hippocampus

Ren

Módy

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

␥-Hydroxybutyrate (GHB) naturally occurs in the brain, but its exogenous administration induces profound effects on the central nervous system in animals and humans. The intracellular signaling mechanisms underlying its actions remain unclear. In the present study, the effects of GHB on the activation (phosphorylation) of mitogen-activated protein kinases (MAP kinases), extracellular signal-regulated kinase 1 and 2 (ERK1/2), were investigated. Acute administration of GHB (500 mg/kg, intraperitoneal) induced a fast and long lasting inhibition of MAP kinase phosphorylation in both frontal cortex and hippocampus. The reduced MAP kinase phosphorylation was observed in the CA1 and CA3 areas but not in the dentate gyrus. Pretreatment with the specific ␥-aminobutyric acid, type B (GABA B ), receptor antagonist CGP56999A (20 mg/kg, intraperitoneal) prevented the action of GHB, and the effect of GHB was mimicked by baclofen, a selective GABA B receptor agonist, whereas the high affinity GHB receptor antagonist NCS-382 (200 mg/kg, intraperitoneal) had no effect on GHB-inhibited MAP kinase phosphorylation. Moreover, the GHB dehydrogenase inhibitor valproate (500 mg/kg, intraperitoneal), which inhibits the conversion of GHB into GABA, failed to block the effect of GHB on MAP kinase phosphorylation. Altogether, these data suggest that GHB, administered in vivo, reduces MAP kinase phosphorylation via a direct activation of GABA B receptors by GHB. In contrast, GHB (10 mM for 15 min) was found ineffective on MAP kinase phosphorylation in brain slices, indicating important differences in the conditions required for the second messenger activating action of GHB.␥-Hydroxybutyrate (GHB) 1 is a natural constituent of the mammalian brain derived from the metabolism of ␥-aminobutyric acid (GABA) (1). Peripherally administered GHB can readily cross the blood-brain barrier and produces significant behavioral, electrophysiological, and biochemical effects. Clinically, GHB has been used as an anesthetic agent (2), in the treatment of alcohol withdrawal and dependence (3), opiate withdrawal (4), and in sleep disorders (5). Recently GHB has emerged as a major recreational drug of abuse, and its abuse or intoxication has been associated with a mild euphoria, respiratory depression, headache, vomiting, agitation, seizures, and even death (6 -8).GHB has been suggested to play a role as a neurotransmitter or neuromodulator in brain (9 -11) and was shown to modulate neuronal excitability and the release of some neurotransmitters in the different brain regions (12)(13)(14)(15)(16). Although the precise mechanisms underlying GHB actions have not been established, accumulating evidence supports that GHB acts via GABA B receptors. For instance, the sedative/hypnotic effect of GHB is entirely mediated by the stimulation of GABA B receptors (17), and GHB can increase the concentrations of neurosteroids in the brain via a GABA B receptor-mediated mechanism (18). Despite these findings, little is known about intracellular signaling pathways possibly re...

show abstract

Continuous sedation during spinal anaesthesia: gamma-hydroxybutyrate vs. propofol

Cited by 30 publications

References 19 publications

Synthesis and Catabolism of γ-Hydroxybutyrate in SH-SY5Y Human Neuroblastoma Cells

Synthesis and Catabolism of γ-Hydroxybutyrate in SH-SY5Y Human Neuroblastoma Cells

Gamma-hydroxy butyric acid: Neurotransmitter, sedative and party drug

γ-Hydroxybutyrate Reduces Mitogen-activated Protein Kinase Phosphorylation via GABAB Receptor Activation in Mouse Frontal Cortex and Hippocampus

Contact Info

Product

Resources

About