Banner
targets (2) transporters (3)
for drugs
Identification
Name Gamma Hydroxybutyric Acid
Accession Number DB01440
Type small molecule
Groups illicit, approved
Description

Gamma Hydroxybutyric Acid, commonly abbreviated GHB, is a therapeutic drug which is illegal in multiple countries. It is currently regulated in the US and sold by Jazz Pharmaceuticals under the name Xyrem. However, it is important to note that GHB is a designated Orphan drug (in 1985). Today Xyrem is a Schedule III drug;
however GHB remains a Schedule I drug and the illicit use of Xyrem falls under penalties of Schedule I. GHB is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits and almost all other living creatures in small amounts. It is used illegally under the street names Juice, Liquid Ecstasy or simply G, either as an intoxicant, or as a date rape drug. Xyrem is a central nervous system depressant that reduces excessive daytime sleepiness and cataplexy in patients with narcolepsy.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
4-Hydroxy-butanoic acid
4-hydroxybutanoate
4-hydroxybutanoic acid
4-Hydroxybutyric acid
gamma-Hydroxybutyric acid
GHB
Juice
Liquid Ecstasy
Sodium oxybate
Salts Not Available
Brand names
Name Company
Xyrem
Brand mixtures Not Available
Categories
  • Adjuvants, Anesthesia
  • Anesthetics, Intravenous
CAS number 591-81-1
Weight Average: 103.0966
Monoisotopic: 103.03951909
Chemical Formula C4H7O3
InChI Key InChIKey=SJZRECIVHVDYJC-UHFFFAOYSA-M
InChI
InChI=1S/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)/p-1
Plain Text
IUPAC Name
4-hydroxybutanoate
SMILES
OCCCC([O-])=O
Plain Text
Mass Spec show (8.17 KB)
Taxonomy
Kingdom Organic
Classes
  • Carboxylic Acids and Derivatives
Substructures
  • Hydroxy Compounds
  • Anions
  • Acetates
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
Pharmacology
Indication Used as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance.
Pharmacodynamics GHB has at least two distinct binding sites in the central nervous system. GHB is an agonist at the newly-characterized GHB receptor, which is excitatory, and it is a weak agonist at the GABAB receptor, which is inhibitory. GHB is a naturally-occurring substance that acts in a similar fashion to some neurotransmitters in the mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire.
Mechanism of action GHB reaches much higher concentrations in the brain and activates GABAB receptors, which are primarily responsible for its sedative effects. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter. Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic,[19] low concentrations stimulate dopamine release via the GHB receptor.[20] Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut.[21] After an initial phase of inhibition, dopamine release is then increased via the GHB receptor. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant GABAB receptor activation and activates predominantly the GHB receptor, leading to wakefulness.
Absorption Not Available
Volume of distribution
  • 190 to 384 mL/kg
Protein binding Not Available
Metabolism Not Available
Route of elimination Animal studies indicate that metabolism is the major elimination pathway for sodium oxybate, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water. Fecal and renal excretion is negligible. 5% renal elimination.
Half life 30 to 60 minutes
Clearance
  • apparent oral cl=9.1 mL/min/kg [healthy adults receiving a single oral dose of 25 mg/kg]
  • 4.5 mL/min/kg [cirrhotic patients without ascites receiving a single oral dose of 25 mg/kg]
  • 4.1 mL/min/kg [cirrhotic patients with ascites receiving a single oral dose of 25 mg/kg]
Toxicity At higher doses, GHB may induce nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Jazz pharmaceuticals
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Xyrem 500 mg/ml oral solution 5.33 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7765106 2004-06-16 2024-06-16
United States 6780889 2000-07-04 2020-07-04
Canada 2355293 2005-08-16 2019-12-22
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 7.11e+02 g/l ALOGPS
logP -0.6 ALOGPS
logP -0.51 ChemAxon
logS 0.77 ALOGPS
pKa (strongest acidic) 4.44 ChemAxon
pKa (strongest basic) -2.4 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 60.36 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 34.64 ChemAxon
polarizability 9.73 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C00989 Link_out
PubChem Compound 3037032 Link_out
PubChem Substance 46507548 Link_out
ChemSpider 2300886 Link_out
ChEBI 16724 Link_out
ChEMBL 16724 Link_out
Therapeutic Targets Database DAP001522 Link_out
PharmGKB PA10819 Link_out
Wikipedia http://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid Link_out
ATC Codes
  • N01AX11
  • N07XX04
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Gamma-hydroxybutyrate receptor

Pharmacological action: yes
Actions: agonist

References:
  1. Castelli MP, Mocci I, Pistis M, Peis M, Berta D, Gelain A, Gessa GL, Cignarella G: Stereoselectivity of NCS-382 binding to gamma-hydroxybutyrate receptor in the rat brain. Eur J Pharmacol. 2002 Jun 20;446(1-3):1-5. Pubmed
  2. Castelli MP, Ferraro L, Mocci I, Carta F, Carai MA, Antonelli T, Tanganelli S, Cignarella G, Gessa GL: Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of gamma-hydroxybutyric acid. J Neurochem. 2003 Nov;87(3):722-32. Pubmed

2. Gamma-aminobutyric-acid receptor subunit beta-1

Pharmacological action: yes
Actions: agonist

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P18505 Link_out
Gene: GABRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Maitre M, Humbert JP, Kemmel V, Aunis D, Andriamampandry C: [A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]. Med Sci (Paris). 2005 Mar;21(3):284-9. Pubmed
Transporters

1. Monocarboxylate transporter 2

Actions: inhibitor

Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. MCT2 is a high affinity pyruvate transporter

UniProt ID: O60669 Link_out
Gene: SLC16A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lin RY, Vera JC, Chaganti RS, Golde DW: Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. J Biol Chem. 1998 Oct 30;273(44):28959-65. Pubmed

2. Monocarboxylate transporter 1

Actions: inhibitor

Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate

UniProt ID: P53985 Link_out
Gene: SLC16A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lin RY, Vera JC, Chaganti RS, Golde DW: Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. J Biol Chem. 1998 Oct 30;273(44):28959-65. Pubmed

3. Monocarboxylate transporter 4

Actions: substrate

Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate

UniProt ID: O15427 Link_out
Gene: SLC16A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Manning Fox JE, Meredith D, Halestrap AP: Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol. 2000 Dec 1;529 Pt 2:285-93. Pubmed
Comments
Drug created on July 31, 2007 07:09 / Updated on February 08, 2013 16:20