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gamma-Butyrolactone

Names
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
3D model (JSmol)	Interactive image
ChEBI	CHEBI:42639
ChEMBL	ChEMBL95681
ChemSpider	7029
DrugBank	DB04699
ECHA InfoCard	100.002.282
KEGG	C01770
PubChem CID	7302
RTECS number	LU3500000
UNII	OL659KIY4X
CompTox Dashboard (EPA)	DTXSID6020224
InChI InChI=1S/C4H6O2/c5-4-2-1-3-6-4/h1-3H2Key: YEJRWHAVMIAJKC-UHFFFAOYSA-N InChI=1/C4H6O2/c5-4-2-1-3-6-4/h1-3H2Key: YEJRWHAVMIAJKC-UHFFFAOYAC
SMILES O=C1OCCC1
Properties
Chemical formula	C4H6O2
Molar mass	86.090 g·mol
Appearance	Colorless oily liquid
Density	1.1286 g/mL (15 °C), 1.1296 g/mL (20 °C)
Melting point	−43.53 °C (−46.35 °F; 229.62 K)
Boiling point	204 °C (399 °F; 477 K)
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
Occupational safety and health (OHS/OSH):
Main hazards	Harmful
Flash point	98 °C (closed cup)
Lethal dose or concentration (LD, LC):
LD50 (median dose)	17.2 mL/kg (orally, rat)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Y verify (what is  ?) 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.

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. Y-aminobutryic acid (GABA) can also be converted into GBL via a quite simple Sandmeyer Reaction: with the addition of sodium nitrite and then acidified with an appropriate acid like HCl(aq). The acidification allows the sodium nitrite to act as nitrous acid, in laymen's terms, and through an intermediary reaction (converting GABA, an amine, to its diazatonium salt, which is then hydrolyzed leaving behind a hydroxyl group where the amino group was) form Y-Butyrolactone. The resulting GBL is simply combined with a stoichometricly correct amount of NaOH resulting in NaGHB; aka sodium Y-hydroxybutyrate.

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.

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

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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.

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.

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.

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

Metabolism takes place in stomach and blood plasma. The duration and onset of GBL is shorter and has a faster onset than GHB. Otherwise, effects are similar to GHB, although weight for weight it 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.

Excessive use

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). At higher doses it acts like a sedative and can make the user unconscious very quickly.

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 dependant 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 roughly 1.4 g of GHB, 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 stale water or burnt plastic.

Legal status of GBL

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. It is not illegal for an individual to possess GBL in Canada.

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.

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.

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 1kg of GBL) is punishable by up to life imprisonment and/or an $825000 fine.

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.

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

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.

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

See also

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

References

1. Merck Index, 12th Edition, 1632.
2. Lide, David R., ed. (2009-06-03). [[CRC Handbook of Chemistry and Physics]] (90th ed.). Boca Raton, Florida: CRC Press. ISBN 1420090844. Retrieved 2011-07-18. {{cite book}}: URL–wikilink conflict (help)
3. Vose J, Tighe T, Schwartz M, Buel E (2001). "Detection of gamma-butyrolactone (GBL) as a natural component in wine". Journal of Forensic Sciences. 46 (5): 1164–7. PMID 11569560. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
4. Metsger, L.; Bittner, S. Autocatalytic Oxidation of Ethers with Sodium Bromate, Tetrahedron 2000, 56, 1905-1910
5. Sassenbroek, Van; De Paepe, P; Belpaire, FM; Buylaert, WA (June 2007). "Characterization of the pharmacokinetic and pharmacodynamic interaction between gamma-hydroxybutyrate and ethanol in the rat". Toxicological Sciences. 73 (2): 270–8. doi:10.1093/toxsci/kfg079. PMID 12700396.
6. Meyer, Jerrold (2005). Psychopharmacology: Drugs, the Brain and Behavior. Sinauer. p. 370. ISBN 0-87893-534-7. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
7. http://www.usdoj.gov/ndic/pubs4/4532/4532p.pdf
8. http://www.psychoactive.org.uk/GHB/addiction.htm
9. http://www.adanz.org.nz/Helpline/Subnav/Drug%20Information/ghb
10. http://www.crew2000.org.uk/news/9/91/GHB-GBL-Dependancy.html
11. The Misuse of Drugs Act 1971 (Amendment) Order 2009 http://www.opsi.gov.uk/si/si2009/draft/ukdsi_9780111486610_en_1
12. GBL
13. http://www.riksdagen.se/Webbnav/index.aspx?nid=3120&doktyp=betankande&bet=2010/11:SoU5
14. LAW AND JUSTICE LEGISLATION AMENDMENT (SERIOUS DRUG OFFENCES AND OTHER MEASURES) ACT 2005 NO. 129, 2005 - SCHEDULE 1 http://www.austlii.edu.au/au/legis/cth/num_act/lajladoaoma2005722/sch1.html
15. Information Bulletin: GHB Analogs; GBL, BD, GHV, and GVL
16. section 7c of chapter B of part A of the 1st appendix of the Dangerous Drugs Act 1973 http://www.nevo.co.il/Law_word/law01/P170_001.doc

External links

• Erowid on GBL
• BBC News story: The paint stripper drug that kills, October 7, 2005.
• “All About GHB," a NIDA Neuroscience Consortium and OSPC “Cutting Edge” colloquium (27 June 2000 at the Doubletree hotel, Rockville, MD) Organized by Drs. Jerry Frankenheim and Minda Lynch in response to the rapid ascent of GHB and its precursors, GBL and 1,4-butanediol, as public health concerns.

• Sedatives
• Lactones
• Solvents
• Tetrahydrofurans