Clenbuterol

Clenbuterol

Systematic (IUPAC) name
(RS)-1-(4-Amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethanol
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	C
Legal status	POM (UK) ℞-only (US)
Routes	oral
Pharmacokinetic data
Bioavailability	89-98% orally
Metabolism	sympathetic nervous system
Half-life	36-48 hours
Excretion	feces and urine
Identifiers
CAS number	37148-27-9 Y
ATC code	R03AC14 R03CC13 QG02CA91
PubChem	CID 2783
DrugBank	DB01407
ChemSpider	2681 Y
UNII	XTZ6AXU7KN Y
KEGG	D07713 Y
ChEBI	CHEBI:174690 Y
ChEMBL	CHEMBL49080 Y
Chemical data
Formula	C12H18Cl2N2O
Mol. mass	277.19
SMILES Clc1cc(cc(Cl)c1N)C(O)CNC(C)(C)C
InChI InChI=1S/C12H18Cl2N2O/c1-12(2,3)16-6-10(17)7-4-8(13)11(15)9(14)5-7/h4-5,10,16-17H,6,15H2,1-3H3 Y Key:STJMRWALKKWQGH-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Clenbuterol, marketed as Spiropent, Ventipulmin, and also generically as clenbuterol, is a sympathomimetic amine used by sufferers of breathing disorders as a decongestant and bronchodilator. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier. It is most commonly available as the hydrochloride salt, clenbuterol hydrochloride.

Effects and dosage

Clenbuterol is a β2 agonist with some structural and pharmacological similarities to epinephrine and salbutamol, but its effects are more potent and longer-lasting as a stimulant and thermogenic drug. It causes an increase in aerobic capacity, central nervous system stimulation, blood pressure, and oxygen transportation. It increases the rate at which body fat is metabolized while increasing the body's BMR. It is commonly used for smooth muscle-relaxant properties as a bronchodilator and tocolytic.

Clenbuterol is also prescribed for treatment of horses, but equine use is usually the liquid form.

Human use

Clenbuterol is approved for use in some countries, via prescription only, as a bronchodilator for asthma patients.^[1]

Legal status

Clenbuterol is not an ingredient of any therapeutic drug approved by the US Food and Drug Administration^[1] and is now banned for IOC-tested athletes.^[2] In the US, administration of clenbuterol to any animal that could be used as food for human consumption is banned by the FDA.^[3]

Weight-loss drug

Although often used by bodybuilders in their "cut" periods, the drug has been more recently known to the mainstream, particularly through publicised stories of use by celebrities such as Victoria Beckham,^[2] Britney Spears, and Lindsay Lohan,^[4] for its off-label use as a weight-loss drug similar to usage of other sympathomimetic amines such as ephedrine, despite the lack of sufficient clinical testing either supporting or negating such use.

Notable cases of use as performance-enhancing drug

As a β2 sympathomimetic, clenbuterol has also been used as a performance-enhancing drug.

A three-year suspension for taking clenbuterol kept sprinter Katrin Krabbe from competing in the 1992 Summer Olympics, and effectively ended her athletic career.^{[5][6] [7]}

In 2006, San Francisco Giants pitcher Guillermo Mota, while a member of the New York Mets, received a 50-game suspension after testing positive for clenbuterol.^[8] In 2012, MLB officials announced they were again suspending Mota for 100 games due a positive test for clenbuterol.^[9]

American swimmer Jessica Hardy tested positive at the US trials in 2008. She was subject to a one-year suspension, having claimed she unknowingly took the drug in a contaminated food supplement. Former New York Mets clubhouse employee Kirk Radomski admitted in his plea deal to distributing clenbuterol to dozens of current and former Major League Baseball players and associates.^[10] After finishing fourth in the K-2 1000-m event at the 2008 Summer Olympics in Beijing, Polish sprint canoer Adam Seroczyński was disqualified for taking this drug, and Chinese cyclist Li Fuyu tested positive for it at the Dwars door Vlaanderen race in Belgium on March 24, 2010.^[11]

In 2010, St. Louis Cardinals minor-league shortstop Lainer Bueno received a 50-game suspension for the 2011 season as a result of testing positive for clenbuterol.^[12] Cyclist Alberto Contador of Spain was banned for two years from professional cycling after testing positive for the drug at the 2010 Tour de France.^[13] He was later stripped of the 2010 title of the Tour de France and the 2011 title of the Giro d'Italia.^[14] CAS found that Contador probably tested positive due to a contaminated food supplement.^[15]

In 2011, players of the Mexico national football team were found with clenbuterol in their bloodstreams, but were acquitted by WADA after they claimed the clenbuterol came from contaminated food. FIFA has also claimed 109 players from the Under-17 World Cup in Mexico tested positive for this drug, because Mexican meat is contaminated.^[16]

In 2013, Mexican boxer Erik Morales was suspended for two years after testing positive for clenbuterol.^[17]

Side effects and dangers

Clenbuterol can cause these side effects:

• Nervousness
• Thyrotoxicosis
• Tachycardia
• Subaortic stenosis
• Low blood pressure
• High blood pressure

Overdosage

Excessive use over the recommended dose of about 120 μg can cause muscle tremors, headache, dizziness, and gastric irritation. Persons self-administering the drug for weight loss or to improve athletic performance have experienced nausea, vomiting, diaphoresis, palpitations, tachycardia, and myocardial infarction. Use of the drug may be confirmed by detecting its presence in semen or urine.^[18]

Food contamination

Clenbuterol is occasionally referred to as "bute" and this risks confusion with phenylbutazone, also called "bute". Phenylbutazone, which is a drug also used with horses, was tested for in the 2013 European meat adulteration scandal.^[19]

Intended to result in leaner meat with a higher muscle-to-fat ratio, the use of clenbuterol has been banned in meat since 1991 in the USA and since 1996 in the European Union. The drug is banned due to health concerns about symptoms noted in consumers. These include increased heart rate, muscular tremors, headaches, nausea, fever, and chills. In the majority of cases, these adverse symptoms are temporary.^[20]

Clenbuterol is a growth-promoting drug in the β-agonist class of compounds. It is not licensed for use in China^[21] or the United States^[22] or the EU^[23] for food producing animals, but some countries have approved it for animals not used for food, and a few countries have approved it for therapeutic uses in food-producing animals.

Not just athletes are affected by contamination. In Portugal, 50 people were reported as affected by clenbuterol in liver and pork between 1998 and 2002, while in 1990, veal liver was suspected of causing clenbuterol poisoning in 22 people in France and 135 people in Spain.^[24]

In September 2006, over 330 people in Shanghai were reported to have food poisoning by eating clenbuterol-contaminated pork that had been fed to the animals to keep the meat lean.^[25]

In February 2009, at least 70 people in one Chinese province (Guangdong) suffered food poisoning after eating pig organs believed to contain clenbuterol residue. The victims complained of stomachaches and diarrhea after eating pig organs bought in local markets.^[26][27]

In March 2011, China's Ministry of Agriculture said the government would launch a one-year crackdown on illegal additives in pig feed, after a subsidiary of Shuanghui Group, China's largest meat producer, was exposed for using clenbuterol-contaminated pork in its meat products. A total of 72 people in central Henan Province, where Shuanghui is based, were taken into police custody for allegedly producing, selling or using clenbuterol.^[28] The situation has dramatically improved in China since September 2011, when a ban of clenbuterol was announced by China’s Ministry of Agriculture.^[29]

Authorities around the world appear to be issuing stricter food safety requirements, such as the Food Safety Modernization Act in the United States, Canada’s revision of their import regulations, China’s new food laws published since 2009, South Africa's new food law, and many more global changes and restrictions. The issue of intentional product adulteration for financial gain, using an ingredient that can be easily purchased on the internet in tablet, syrup, or injection formulas, is a constant reminder that verification, inspection, and certification of food safety is absolutely essential in the marketplace.^[30]

Veterinary use

The US and the EU prohibit the use of clenbuterol in food-producing animals. It is, however, used in other parts of the world for the treatment of allergic respiratory disease in horses, as it is a bronchodilator. A common trade name is Ventipulmin. It can be used both orally and intravenously. It is also used in cattle to relax the uterus in cows, usually at the time of parturition.^[31] It is also a nonsteroidal anabolic and metabolism accelerator,^{[citation needed]} through a mechanism not well understood. Although illegal, its ability to increase the muscle-to-body fat ratio makes its use in livestock popular to obtain leaner meats.^{[citation needed]}

References

External links

• Charles F. Kearns, Kenneth H. McKeever, Karyn Malinowski, Maggie B. Struck, and Takashi Abe (2001). "Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent". J Appl Physiol 91 (5): 2064–2070. PMID 11641345.