gamma-Butyrolactone

gamma-Butyrolactone
IUPAC name Dihydrofuran-2(3H)-one
Other names GBL, butyrolactone, 1,4-lactone, 4-butyrolactone, 4-hydroxybutyric acid lactone, gamma-hydroxybutyric acid lactone, and oxolan-2-one
Identifiers
CAS number	96-48-0 Y
PubChem	7302
ChemSpider	7029 Y
UNII	OL659KIY4X Y
DrugBank	DB04699
KEGG	C01770 Y
ChEBI	CHEBI:42639 Y
ChEMBL	CHEMBL95681 Y
RTECS number	LU3500000
Jmol-3D images	Image 1
SMILES O=C1OCCC1
InChI InChI=1S/C4H6O2/c5-4-2-1-3-6-4/h1-3H2 Y Key: YEJRWHAVMIAJKC-UHFFFAOYSA-N Y InChI=1/C4H6O2/c5-4-2-1-3-6-4/h1-3H2 Key: YEJRWHAVMIAJKC-UHFFFAOYAC
Properties
Molecular formula	C4H6O2
Molar mass	86.089 g mol−1
Appearance	Colorless oily liquid
Density	1.1286 g/mL (15 °C), 1.1296 g/mL (20 °C)
Melting point	-43.53 °C, 230 K, -46 °F
Boiling point	204 °C, 477 K, 399 °F
Solubility in water	Miscible
Solubility	soluble in CCl4, methanol, ethanol, acetone, benzene, ethyl ether
Acidity (pKa)	4.5
Refractive index (nD)	1.435, 1.4341 (20 °C)
Viscosity	1.7 cp (25 °C)
Hazards
R-phrases	R22 R36
S-phrases	S26 S36
Main hazards	Harmful
Flash point	98 °C (closed cup)
LD50	17.2 mL/kg (orally, rat)
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

gamma-Butyrolactone (γ-butyrolactone or GBL) is a hygroscopic colorless oily liquid with a weak characteristic odor and is soluble in water. GBL is a common solvent and reagent in chemistry and is used as an aroma compound, as a stain remover, as a superglue remover, as a paint stripper, and as a solvent in some wet aluminium electrolytic capacitors. In humans it acts as a prodrug for GHB, and it is used as a recreational intoxicant with effects similar to alcohol.

Occurrence

GBL has been found in extracts from samples of unadulterated wines. This finding indicates that GBL is a naturally occurring component in some wines and may be present in similar products. The concentration detected was approximately 5 μg/mL and was easily observed using a simple extraction technique followed by GC/MS analysis.

Preparation

GBL can be synthesized from gamma-hydroxybutyric acid (GHB) by removal of water or by distillation from such a mixture. It may also be obtained via oxidation of tetrahydrofuran (THF). One such process, which affords GBL in yields of up to 80%, utilises bromine generated in situ from an aqueous solution of sodium bromate and potassium hydrogen sulfate. Another process can proceed by using commercially-available calcium hypochlorite in the presence of activating acetic acid and an appropriate solvent such as acetonitrile. γ-Aminobutryic acid (GABA) can also be converted into GBL via a quite simple Sandmeyer reaction.^{[citation needed]}

Chemistry

GBL is a lactone. It is hydrolyzed under basic conditions, for example in a sodium hydroxide solution into sodium gamma-hydroxybutyrate, the sodium salt of gamma-hydroxybutyric acid. Under acidic conditions it forms an equilibrium mixture of both compounds. These compounds then may go on to form a polymer. When treated with a non-nucleophilic base, like lithium diisopropylamide, GBL can become an alpha-carbon nucleophile. Related compound caprolactone can be used to make a polyester in this manner.

Pharmacology

Main article: gamma-hydroxybutyrate#Pharmacology

GBL is not active in its own right; its mechanism of action stems from its identity as a prodrug of GHB.

The hypnotic effect of GHB is enhanced by combination with alcohol. A 2003 rat study showed that GBL in combination with ethanol showed a potentiated hypnotic effect, as the sleep-timing measure was longer than both of the individual components combined.

Pharmacokinetics

GBL is rapidly converted into GHB by lactonase enzymes found in the blood. GBL is more lipophilic (fat soluble) than GHB, and so is absorbed faster and has higher bioavailability; the paradox is that this can mean that GBL has a faster onset of effects than GHB itself, even though it is a prodrug. The levels of lactonase enzyme can vary between individuals, meaning that first-time users can show unpredictable results, even from small doses. In many this manifests as slow onset of effects, followed by headaches, semi-consciousness which is distinct from GBL sleep in normal users. If the user decides to try again at a later date, they appear to be able to enjoy the effects normally. Because of these pharmacokinetic differences, GBL tends to be more potent and faster-acting than GHB, but has a shorter duration; whereas the related compound 1,4-butanediol (1,4-B) tends to be slightly less potent, slower to take effect but longer-acting than GHB.

Metabolic pathway of 1,4-butanediol, GBL and GHB.

Use as a nutritional supplement

Due to its property of being a prodrug of GHB, GBL was sold as a nutritional supplement after the scheduling of GHB, under the names Revivarant and Renewtrient in the U.S. at least until the end of 1999.

GBL (as well as GHB), when taken internally in therapeutic doses without the presence of other drugs (especially alcohol, as mixing the two can be fatal), has been shown to elevate growth hormone levels in humans to at least 5 times the baseline.^{[citation needed]}

Recreational use

GBL is a prodrug of GHB. To bypass GHB restriction laws, home synthesis kits were introduced to transform GBL and/or 1,4-B into GHB. GBL can also be used as a recreational drug by itself.

Jugs of seized GBL.

FDA warning against products containing GHB and its prodrugs, such as GBL.

GBL overdose can cause irrational behaviour, severe sickness, coma and death.

Metabolism takes place in stomach and blood plasma. Both the duration and onset of GBL are shorter than of GHB. Otherwise, effects are similar to GHB, although weight for weight GBL is significantly more powerful due to being absorbed faster and its higher bioavailability, meaning dosage must be lowered accordingly. If taken undiluted by mouth, GBL can cause esophageal and gastro-intestinal irritation. It is possible for oral ingestion of GBL to cause nausea and other similar problems, possibly more so than with GHB.

Dangers

GHB (gamma hydroxybutyrate) and GBL (gamma butyrolactone) are substances which are often used as recreational drugs. GHB has two effects, at low doses it has a euphoric effect (which is why it is sometimes referred to as liquid ecstasy). GHB also has a sedative effect and at higher doses it can cause unconsciousness.

There have been news reports of several deaths associated with GBL.

Addictiveness

Frequent use of GHB/GBL, even when taken long-term and in moderate doses, does not appear to cause significant physical dependency in the greater majority of its users. In many people, quitting or temporarily abstaining from use of the drugs is achieved with minimal or no difficulty. However, when consumed in excessive amounts with a high frequency of dosing, physical and psychological dependence can develop.

Frequent use of alcohol (which induces similar effects) can directly translate to physical and usually psychological addiction, where the heavy user can suffer painful and even life-threatening withdrawals.

There are some reports of GHB/GBL users adopting a '24/7' dosing regime. This is where the user has become tolerant to the effects of the drug, increasing the dosage and frequency of dosage simply to avoid withdrawal symptoms.

For those users who do report withdrawal symptoms upon quitting the use of GHB/GBL, symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience insomnia and sleep-related problems, whereas heavy, prolonged use can cause severe withdrawal symptoms similar to Benzodiazepine withdrawal syndrome (BWS).

Dose

A milliliter of pure GBL metabolizes to the equivalent 1.65g of NaGHB, the common form, so doses are measured in the single milliliter range, either taken all at once or sipped over the course of a night. GBL has a distinctive taste and odour, described as being comparable to stale water, synthetic melon aroma or burnt plastic. This differs significantly from GHB, which is described as having a decidedly "salty" taste.

Legal status of GBL

Australia: GBL is a border controlled substance and is illegal to import into Australia without a permit. The importation of a commercial quantity of a border controlled drug (over 1 kg of GBL) is punishable by up to life imprisonment and/or an $825,000 fine.

Canada: GBL is a Controlled Substance under Schedule VI of the "Controlled Drugs and Substances Act" in Canada. Schedule VI of the "Controlled Drugs and Substances Act" requires vendors to collect information regarding purchases of GBL. The Act also prohibits the import and export of GBL into or out of Canada classifying it as either an indictable offense punishable with up to 10 years in prison or an offense punishable on summary conviction liable to imprisonment for up to eighteen months. It is not illegal for an individual to possess GBL in Canada.^{[citation needed]}

Germany: GBL is not listed in the narcotics law, but its distribution is controlled. Possession is not illegal, but may be punished according to the Medicines Act, when intended to be sold for human consumption or synthesis of GHB. In recent years, an increase of GBL consumption has been observed due to the prohibition of GHB.

Hong Kong SAR: GBL is a dangerous drug controlled under Schedule 1 of the Dangerous Drugs Ordinance, Cap.134 (with exemption clause at Paragraph 16D). Any person who is found to have in his possession of it not in accordance with this Ordinance can be liable, on conviction upon indictment, a fine of HK$1,000,000 and to imprisonment for 7 years.

Israel: GBL was classified as a proscribed substance from 2007.

The Netherlands: GBL can be freely bought as a cleaning agent. Retailers do not need a licence to sell the substance.

Poland: GBL is not classified as a drug and can be purchased in chemistry shops as a solvent.

Sweden: GBL is not classified as a drug but as a health-endangering substance. Although recently passed legislation to enter into force on 1 April 2011 will make it possible to handle narcotics for industrial purposes will enable GBL and 1,4-Butanediol to be classified as controlled substances.

United Kingdom: GBL was classified as a Class C drug from 23 December 2009, with a prison term of up to two years for possession and 14 years for dealing, by the end of 2009.

United States: GBL is regulated as a List 1 controlled chemical. As a GHB analog, it is treated as a controlled substance under Schedule I of the "Controlled Substances Act" if intended for human consumption.

See also

• gamma-Hydroxybutyrate (GHB)
• 1,4-Butanediol (1,4-B)

External links

• Erowid on GBL
• "The paint stripper drug that kills". BBC News. October 7, 2005. 
• "All About GHB," a NIDA Neuroscience Consortium and OSPC "Cutting Edge" colloquium (27 June 2000 at the Doubletree hotel, Rockville, MD)