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Identification
NameGamma Hydroxybutyric Acid
Accession NumberDB01440
Typesmall molecule
Groupsapproved, illicit
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
Synonyms
SynonymLanguageCode
3-carboxypropoxy acidNot AvailableNot Available
4-hydroxy-butyric acidNot AvailableNot Available
4-hydroxybutanoateNot AvailableNot Available
4-hydroxybutanoic acidNot AvailableNot Available
4-Hydroxybutyric acidNot AvailableNot Available
gamma-HydroxybutyrateNot AvailableNot Available
gamma-Hydroxybutyric acidNot AvailableNot Available
GHBNot AvailableNot Available
oxy-n-butyric acidNot AvailableNot Available
γ-Hydroxybutyric acidNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
XyremNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number591-81-1
WeightAverage: 103.0966
Monoisotopic: 103.03951909
Chemical FormulaC4H7O3
InChI KeySJZRECIVHVDYJC-UHFFFAOYSA-M
InChI
InChI=1S/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)/p-1
IUPAC Name
4-hydroxybutanoate
SMILES
OCCCC([O-])=O
Mass Specshow(8.17 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsPrimary Alcohols; Enolates; Carboxylic Acid Salts
Substituentsalcohol
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationUsed as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance.
PharmacodynamicsGHB 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 actionGHB 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.
AbsorptionNot Available
Volume of distribution
  • 190 to 384 mL/kg
Protein bindingNot Available
Metabolism
Route of eliminationAnimal 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 life30 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]
ToxicityAt higher doses, GHB may induce nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7851
Blood Brain Barrier + 0.9171
Caco-2 permeable + 0.5539
P-glycoprotein substrate Non-substrate 0.8415
P-glycoprotein inhibitor I Non-inhibitor 0.981
P-glycoprotein inhibitor II Non-inhibitor 0.9783
Renal organic cation transporter Non-inhibitor 0.9223
CYP450 2C9 substrate Non-substrate 0.8341
CYP450 2D6 substrate Non-substrate 0.9043
CYP450 3A4 substrate Non-substrate 0.7878
CYP450 1A2 substrate Non-inhibitor 0.8141
CYP450 2C9 substrate Non-inhibitor 0.9518
CYP450 2D6 substrate Non-inhibitor 0.9541
CYP450 2C19 substrate Non-inhibitor 0.9642
CYP450 3A4 substrate Non-inhibitor 0.9721
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9884
Ames test Non AMES toxic 0.9331
Carcinogenicity Non-carcinogens 0.7478
Biodegradation Ready biodegradable 0.9967
Rat acute toxicity 1.7448 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9579
hERG inhibition (predictor II) Non-inhibitor 0.97
Pharmacoeconomics
Manufacturers
  • Jazz pharmaceuticals
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Xyrem 500 mg/ml oral solution5.33USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States77651062004-06-162024-06-16
United States67808892000-07-042020-07-04
Canada23552932005-08-162019-12-22
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility7.11e+02 g/lALOGPS
logP-0.6ALOGPS
logP-0.51ChemAxon
logS0.77ALOGPS
pKa (strongest acidic)4.44ChemAxon
pKa (strongest basic)-2.4ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area60.36ChemAxon
rotatable bond count3ChemAxon
refractivity34.64ChemAxon
polarizability9.73ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Joseph Klosa, “Production of nonhygroscopic salts of 4-hydroxybutyric acid.” U.S. Patent US4393236, issued March, 1963.

US4393236
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC00989
PubChem Compound3037032
PubChem Substance46507548
ChemSpider2300886
ChEBI16724
ChEMBL
Therapeutic Targets DatabaseDAP001522
PharmGKBPA10819
WikipediaGamma-Hydroxybutyric_acid
ATC CodesN01AX11N07XX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Gamma-hydroxybutyrate (GHB) receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-hydroxybutyrate (GHB) receptor Q9HAB3 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 2 O60669 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 1 P53985 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Monocarboxylate transporter 4 O15427 Details

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

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Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14