Clenbuterol - Wikipedia

Chemical compound which aids breathing Clenbuterol

Clenbuterol (top),and (R)-(−)-clenbuterol (bottom)
Clinical data
Trade names	Dilaterol, Spiropent, Ventipulmin, others[1]
AHFS/Drugs.com	International Drug Names
Pregnancycategory	C
Routes ofadministration	Oral (tablets, oral solution)
ATC code	R03AC14 (WHO) R03CC13 (WHO) QG02CA91 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	89–98% (orally)
Metabolism	Hepatic (negligible)
Elimination half-life	36–48 hours
Excretion	Feces and urine
Identifiers
IUPAC name (RS)-1-(4-Amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethan-1-ol
CAS Number	37148-27-9 Y
PubChem CID	2783
IUPHAR/BPS	12582
DrugBank	DB01407 Y
ChemSpider	2681 Y
UNII	XTZ6AXU7KN
KEGG	D07713 Y
ChEBI	CHEBI:174690 Y
ChEMBL	ChEMBL49080 Y
CompTox Dashboard (EPA)	DTXSID7022833
ECHA InfoCard	100.048.499
Chemical and physical data
Formula	C12H18Cl2N2O
Molar mass	277.19 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
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
(verify)

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.[2]

It was patented in 1967 and came into medical use in 1977.[3]

Medical uses

[edit]

Clenbuterol is approved for use in some countries as a bronchodilator for asthma.[medical citation needed]

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.[citation needed] It is commonly used for smooth muscle-relaxant properties as a bronchodilator and tocolytic.

It is classified by the World Anti-Doping Agency as an anabolic agent, not as a β2 agonist.[4]

Clenbuterol is prescribed for treatment of respiratory diseases for horses, and as an obstetrical aid in cattle.[5] It is illegal in some countries to use in livestock used for food.[6]

Side effects

[edit]

Clenbuterol can cause these side effects:[7]

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

Overdosage

[edit]

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.[8]

Society and culture

[edit]

Legal status

[edit]

Clenbuterol is not an ingredient of any therapeutic drug approved by the US Food and Drug Administration[citation needed] and is now banned for IOC-tested athletes.[9] In the US, administration of clenbuterol to any animal that could be used as food for human consumption is banned by the FDA.[10][11]

Weight-loss

[edit]

Although often used by bodybuilders during their "cutting" cycles,[12] the drug has been more recently[as of?] known to the mainstream, particularly through publicized stories of use by celebrities such as Victoria Beckham,[9] Britney Spears, and Lindsay Lohan,[13] 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. In 2021, Odalis Santos Mena, a Mexican fitness influencer, died after suffering a cardiac arrest while being anesthetized for a procedure of miraDry, a treatment that uses thermal energy to eliminate underarm sweat glands. The coroner reported that Mena's death was attributed to a combination of Clenbuterol and anesthesia.

In a clinical study performed on young, healthy men, "Clenbuterol increased resting energy expenditure by 21% (P < 0.001), and fat oxidation by 39% (P = 0.006), whereas carbohydrate oxidation was unchanged."[14]

Performance-enhancing drug

[edit] See also: List of doping cases in sport by substance § Clenbuterol

A common misconception about Clenbuterol is that it has anabolic properties, and can increase muscle mass when used in higher dosages. This claim has never been substantiated, and likely originated from equine research.[15] A beta-2 agonist, Clenbuterol has been found to increase short-term work rate and cardiovascular output, and consequently, its anabolic effects in horses can be attributed to exercise output and increased caloric intake. Given its ability to increase basal metabolic rate, maximum heart rate, and exercise output, Clenbuterol has ergogenic properties more closely related to ephedrine or amphetamine.

The notion that Clenbuterol is an anabolic agent likely originated from author and renowned authority on performance-enhancement Dan Duchaine. Duchaine popularized the drug in the bodybuilding community, and was the first to suggest the drug had muscle-building properties. Likewise, Duchaine erred in promoting the drug Gamma-hydroxybutyric acid (GHB) as an anabolic agent, and served time for the unlawful possession and distribution of the drug in the mid-1990s.[16] As of 2011, the World Anti-Doping Agency (WADA) listed Clenbuterol as an anabolic agent, despite the fact there is no evidence to suggest this is the case.[17]

Clenbuterol has also been used as a performance-enhancing drug. One issue is that clenbuterol is a food contaminant in some countries; doping control must distinguish between accidental and deliberate intake.[18][19]

Food contamination

[edit]

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.[20]

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 US 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 several cases in Europe, these adverse symptoms have been temporary.[21]

Clenbuterol is a growth-promoting drug in the β agonist class of compounds. It is not licensed for use in China,[22] the United States,[21] 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, some 330 people in Shanghai suffered from food poisoning after eating clenbuterol-contaminated pork.[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 stomach aches and diarrhea after eating pig organs bought in local markets.[26]

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.[27] The situation has dramatically improved in China since September 2011, when a ban of clenbuterol was announced by China's Ministry of Agriculture.[28]

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.

Veterinary use

[edit]

Clenbuterol is administered as an aerosol for the treatment of allergic respiratory disease in horses as a bronchodilator, and intravenously in cattle to relax the uterus in cows at the time of parturition,[29] specifically to facilitate exteriorisation of the uterus during Caesarian section surgery. It is licensed for obstetrical use in cattle as Planipart Solution for Injection.[30]

See also

[edit]

• Mabuterol (same structure as clenbuterol but one of the chloro groups has been changed to a trifluoromethyl group instead).
• Cimaterol

References

[edit]

1. ^ Center for Veterinary Medicine. "FOIA Drug Summaries - NADA 140-973 VENTIPULMIN® SYRUP - original approval". www.fda.gov. Retrieved 2016-03-10.
2. ^ "874. Clenbuterol (WHO Food Additives Series 38)". www.inchem.org. Retrieved 2016-03-10.
3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 543. ISBN 978-3-527-60749-5.
4. ^ Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, et al. (January 2011). "β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials". Sports Medicine. 41 (1): 39–57. doi:10.2165/11537540-000000000-00000. PMID 21142283. S2CID 189906919.
5. ^ "Presentation". www.noahcompendium.co.uk. Retrieved 2020-01-24.
6. ^ Dowling PM. "Systemic Therapy of Inflammatory Airway Disease". Merck Veterinary Manual. Retrieved 14 November 2018.
7. ^ "Clenbuterol - SteroidAbuse .com". www.steroidabuse.com. Retrieved 2016-03-10.
8. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 325–326.
9. ^ a b Guest K (2007-04-10). "Clenbuterol: The new weight-loss wonder drug gripping Planet Zero". The Independent. London. Archived from the original on 2007-04-08. Retrieved 2007-04-10.
10. ^ FDA's Prohibited Drug List, Food Animal Residue Avoidance & Depletion Program
11. ^ "Animal Drugs @ FDA". www.accessdata.fda.gov. Retrieved 2016-03-10.
12. ^ "Anabolic Steroids and SARMS Handbook for Bodybuilders and Athletes". Retrieved 2019-06-16.
13. ^ "Clenbuterol Weight Loss Hollywood Secret". PRBuzz. London. 2012-05-17. Archived from the original on 2018-07-19. Retrieved 2012-04-10.
14. ^ Jessen S, Solheim SA, Jacobson GA, Eibye K, Bangsbo J, Nordsborg NB, et al. (May 2020). "Beta2 -adrenergic agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR phosphorylation in skeletal muscle of young healthy men". Drug Testing and Analysis. 12 (5): 610–618. doi:10.1002/dta.2755. PMID 31887249. S2CID 209520346.
15. ^ Kearns CF. "Clenbuterol and the Horse Revisisted". Research Gate. The Veterinary Journal. Retrieved 4 April 2020.
16. ^ Assael S. "Dan Duchaine: a founding father of the steroid movement". espn.com. ESPN. Retrieved 4 April 2020.
17. ^ Pluim BM, de Hon O, Staal JB, Limpens J, Kuipers H, Overbeek SE, et al. (January 2011). "β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials". Sports Medicine. 41 (1): 39–57. doi:10.2165/11537540-000000000-00000. PMID 21142283. S2CID 189906919.
18. ^ Guddat S, Fußhöller G, Geyer H, Thomas A, Braun H, Haenelt N, et al. (June 2012). "Clenbuterol - regional food contamination a possible source for inadvertent doping in sports". Drug Testing and Analysis. 4 (6): 534–538. doi:10.1002/dta.1330. PMID 22447758.
19. ^ Velasco-Bejarano B, Velasco-Carrillo R, Camacho-Frias E, Bautista J, López-Arellano R, Rodríguez L (June 2022). "Detection of clenbuterol residues in beef sausages and its enantiomeric analysis using UHPLC-MS/MS: A risk of unintentional doping in sport field". Drug Testing and Analysis. 14 (6): 1130–1139. doi:10.1002/dta.3235. PMC 9303807. PMID 35132808.
20. ^ "Horse meat investigation. Advice for consumers". Enforcement and regulation. Food Standards Agency. Archived from the original on 16 June 2013. Retrieved 19 May 2013.
21. ^ a b "Clenbuterol". Food Safety and Inspection Service (FSIS). July 1995. Archived from the original on 2012-08-29. Retrieved 8 April 2015.
22. ^ "China bans production, sale of clenbuterol to improve food safety". Archived from the original on 2011-10-03. Retrieved 22 August 2012.
23. ^ "Animal Nutrition - Undesirable Substances". European Commission. Archived from the original on 10 August 2012. Retrieved 22 August 2012.
24. ^ "Anti Doping Advisory Notes". Archived from the original on 22 May 2015. Retrieved 22 August 2012.
25. ^ Research Brief: Food Safety in China (PDF). China Environmental Health Project, Woodrow Wilson International Center for Scholars. June 28, 2007. Archived from the original (PDF) on July 7, 2017. Retrieved July 31, 2017.
26. ^ "China: 70 ill from tainted pig organs". CNN. 2009-02-23. Retrieved 2010-04-30.
27. ^ "China to launch one-year crackdown on contaminated pig feed – xinhuanet.com". Xinhua. 2011-03-28. Archived from the original on April 1, 2011. Retrieved 2011-03-29.
28. ^ Bottemiller H (April 26, 2011). "Amid Scandal, China Bans More Food Additives". Food Safety News. Retrieved August 22, 2012.
29. ^ Planipart Solution for Injection 30 micrograms/ml: Uses Archived 2011-07-21 at the Wayback Machine, National Office of Animal Health
30. ^ "Presentation". www.noahcompendium.co.uk. Retrieved 2020-01-24.

Further reading

[edit]

• Kearns CF, McKeever KH, Malinowski K, Struck MB, Abe T (November 2001). "Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent". Journal of Applied Physiology. 91 (5): 2064–70. doi:10.1152/jappl.2001.91.5.2064. PMID 11641345. S2CID 15387373.

v t e Adrenergic receptor modulators
α1	Agonists 6-FNE Amidephrine Buspirone Cirazoline Corbadrine Deoxyepinephrine (epinine, N-methyldopamine) Desglymidodrine Dexisometheptene Dipivefrine Dopamine Droxidopa (L-DOPS) Epinephrine Etilefrine Etilevodopa Ethylnorepinephrine Ibopamine Indanidine Isometheptene L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Melevodopa Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine Oxymetazoline Phenylephrine Phenylpropanolamine Synephrine Tetryzoline Tiamenidine XP21279 Xylometazoline Antagonists Abanoquil Ajmalicine Alfuzosin Anisodamine Anisodine Atiprosin Atypical antipsychotics (e.g., brexpiprazole, clozapine, olanzapine, quetiapine, risperidone) Benoxathian Beta blockers (e.g., adimolol, amosulalol, arotinolol, carvedilol, eugenodilol, labetalol) Buflomedil Bunazosin Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., acetergamine, ergotamine, dihydroergotamine, lisuride, nicergoline, terguride) Etoperidone Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione) Piperoxan Prazosin Quinazosin Quinidine Silodosin Spegatrine Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine) Trimazosin Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Urapidil WB-4101 Zolertine
α2	Agonists (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Clonidine Corbadrine Deoxyepinephrine (epinine, N-methyldopamine) Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Droxidopa (L-DOPS) Etilevodopa Ergotamine Epinephrine Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Ibopamine Lofexidine Medetomidine Melevodopa Methyldopa Mivazerol Moxonidine Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan PS75 Rezatomidine Rilmenidine Romifidine Talipexole Tasipimidine Tetryzoline Tiamenidine Tizanidine Tolonidine Urapidil Vatinoxan XP21279 Xylazine Xylometazoline Antagonists 1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, zotepine) Azapirones (e.g., buspirone, gepirone, ipsapirone, tandospirone) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan Ketanserin Lisuride mCPP Mianserin Mirtazapine NAN-190 Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine Setiptiline Spegatrine Spiroxatrine Sunepitron Terguride Tolazoline Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Yohimbine
β	Agonists Abediterol Alifedrine Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Carmoterol Cimaterol Clenbuterol Colterol Corbadrine Denopamine Deoxyepinephrine (epinine, N-methyldopamine) Dipivefrine Dobutamine Dopamine Dopexamine Droxidopa (L-DOPS) Epinephrine Etafedrine Etilefrine Etilevodopa Ethylnorepinephrine Eugenodilol Fenoterol Formoterol Hexoprenaline Higenamine Ibopamine Indacaterol Isoetarine Isoprenaline Isoxsuprine L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Levosalbutamol Lubabegron Mabuterol Melevodopa Methoxyphenamine Methyldopa Mirabegron Norepinephrine Orciprenaline Oxyfedrine PF-610355 Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Vibegron Vilanterol Xamoterol XP21279 Zilpaterol Zinterol Antagonists Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Bufuralol Bunitrolol Bunolol Bupranolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levomoprolol Medroxalol Mepindolol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nebivolol Nifenalol Nipradilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Penbutolol Pindolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol Talinolol Tazolol Tertatolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Xibenolol Xipranolol
See also: Receptor/signaling modulators Dopaminergics Serotonergics Monoamine reuptake inhibitors Monoamine releasing agents Monoamine metabolism modulators Monoamine neurotoxins

v t e Drugs for obstructive airway diseases: asthma/COPD (R03)
Adrenergics, inhalants	Short-acting β2 agonists Bitolterol Carbuterol Fenoterol Isoetarine Pirbuterol Procaterol Reproterol Rimiterol Salbutamol (albuterol)#/Levosalbutamol (levalbuterol) Terbutaline Tulobuterol Long-acting β2 agonists Bambuterol Clenbuterol Formoterol/Arformoterol Salmeterol Ultra-long-acting β2 agonists Abediterol Carmoterol Indacaterol Olodaterol Vilanterol Other Clorprenaline Ephedrine (+theophylline, +theophylline/phenobarbital, theophylline/hydroxyzine) Epinephrine# Etafedrine Hexoprenaline Isoprenaline (isoproterenol) Methylephedrine Orciprenaline (metaproterenol) Racephedrine
Glucocorticoids	Beclometasone# Betamethasone# Budesonide Ciclesonide Flunisolide Fluticasone propionate Mometasone Triamcinolone
Anticholinergics/muscarinic antagonist	Aclidinium bromide Glycopyrronium bromide Ipratropium bromide# Oxitropium bromide Tiotropium bromide Umeclidinium bromide
Mast cell stabilizers	Cromoglicate Nedocromil
Xanthines	Acefylline Ambuphylline Aminophylline Bamifylline Choline theophyllinate Doxofylline Enprofylline Etamiphylline Proxyphylline Theophylline
Eicosanoid inhibition	Leukotriene antagonists Montelukast Pranlukast Zafirlukast Arachidonate 5-lipoxygenase inhibitors Zileuton Thromboxane receptor antagonists Ramatroban Seratrodast Non-xanthine PDE4 inhibitors Ibudilast Roflumilast
Others/unknown	Amlexanox Ensifentrine Eprozinol Fenspiride‡ Omalizumab
Combination products	Aclidinium bromide/formoterol Beclometasone/formoterol Beclometasone/formoterol/glycopyrronium bromide Budesonide/formoterol Budesonide/glycopyrronium bromide/formoterol Fluticasone furoate/umeclidinium bromide/vilanterol Fluticasone furoate/vilanterol Fluticasone propionate/salmeterol Glycopyrronium bromide/formoterol Indacaterol/glycopyrronium bromide Indacaterol/glycopyrronium bromide/mometasone Indacaterol/mometasone Ipratropium bromide/salbutamol Mometasone/formoterol Salbutamol (albuterol)/budesonide Theophylline/ephedrine Theophylline/ephedrine/hydroxyzine Theophylline/ephedrine/phenobarbital Umeclidinium bromide/vilanterol
#WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III

Authority control databases: National	Germany