Today, clenbuterol is primarily associated with pre-competition weight cutting and doping scandals. However, it was developed as a medicine for bronchial obstruction, and it is still registered for humans in some countries and for animals in many others. The editors tell for what medical purpose clenbuterol appeared, where and how it is used officially, and why its use in animal husbandry has become a health care problem.
Origin: long-acting bronchodilator
Clenbuterol was synthesized in the 1960s as part of the search for selective beta-2-adrenomimetics, drugs that dilate the bronchi but have less effect on the heart than non-selective precursors such as isoprenaline. The developer was the German pharmaceutical company Boehringer Ingelheim.
Compared to the first short-acting beta-2 agonists, clenbuterol had two advantages: high activity when taken orally and a long half-life, which allowed it to be taken only twice a day.
The drug has received registration in a number of European and Asian countries under various trade names, the most famous being Spiropent. The main indications are bronchial asthma and chronic obstructive pulmonary diseases with bronchospasm.
Clenbuterol has never been approved for human use by the Food and Drug Administration (FDA) in the United States. It is registered there only as a veterinary drug for horses.
Application in human medicine
In countries where clenbuterol is approved for humans, it is used as an oral bronchodilator. The instructions for such drugs provide very small doses - in micrograms: for adults, usually 20 mcg twice a day. For comparison, salbutamol in tablets is dosed in milligrams.
Currently, the role of clenbuterol in pulmonology is limited. Modern guidelines for the treatment of asthma and COPD prefer inhaled beta-2-agonists — they act directly on the bronchi and in much smaller systemic doses, therefore causing fewer side effects.
Systemic administration in the form of tablets or syrup inevitably affects all tissues with beta-2 receptors. That is why side effects in medical use include tremors, palpitations, restlessness, muscle cramps.
Contraindications indicated in the instructions include thyrotoxicosis, hypertrophic obstructive cardiomyopathy, tachyarrhythmias. The drug is used with caution in cardiovascular diseases, diabetes and hypokalemia.
| Sphere | Indications | Status |
|---|---|---|
| Human medicine | Asthma, COPD with bronchospasm | Registered in some countries; not approved in the US |
| Veterinary (horses) | Obstructive diseases of the respiratory tract | US and EU approved for horses, not for food animals |
| Veterinary (Cattle) | Tocolysis during calving | Authorized in the EU as a single veterinary intervention |
| Animal husbandry | Growth stimulator ("repartitioning agent") | Banned in EU, USA, China and many other countries |
Veterinary use
The most stable field of application of clenbuterol has become veterinary medicine. In horses, it is used to treat recurrent airway obstruction, a condition similar to human asthma. A review by Kearns and McKeever (2009) in The Veterinary Journal examines the pharmacology and effects of the drug in horses in detail.
In the USA, the equine veterinary drug has official FDA approval with an express prohibition of use in food animals. The label also warns people to avoid contact with the drug.
In the European Union, clenbuterol is used, in addition to horses, in veterinary obstetric practice — as a tocolytic that relaxes the uterus of cows during difficult calving. This is a one-time intervention under the supervision of a veterinarian.
At the same time, equestrian sports have their own anti-doping rules, and clenbuterol in competition horses is also monitored because it can affect performance.
Animal husbandry: from "lean meat" to food poisoning
In the 1980s, it became clear that beta-2-agonists, in particular clenbuterol, in doses significantly exceeding therapeutic ones, change the composition of animal carcasses: they reduce fat and increase the proportion of muscles. Mersmann (1998) describes the mechanisms behind this "repartitioning" effect.
The illegal use of clenbuterol as a growth stimulant in livestock has led to a number of mass food poisonings in humans. The most famous outbreaks occurred in Spain and France in the early 1990s after consumption of animal liver containing residues of the drug. The victims had tremors, palpitations, headaches and muscle cramps.
In response, the EU introduced a ban on the use of beta-agonists to stimulate the growth of farm animals (Council Directive 96/22/EU) and a residue monitoring system. Similar bans are in force in the USA, China and many other countries.
However, the problem still persists in some regions. This is also important for sports: anti-doping laboratories recorded cases related to the alleged consumption of contaminated meat (Guddat et al., 2012).
Experimental medical research
Clenbuterol's anabolic effects in animals prompted researchers to test whether it could help patients with muscle loss. A small study by Maltin et al (1993) in orthopedic patients after knee surgery showed a faster recovery of relative muscle strength.
The most famous clinical experiment was the so-called Harefield protocol. Birks et al. (2006) published in the New England Journal of Medicine the results of the treatment of severe heart failure: patients were installed with a device for mechanical support of the left ventricle and carried out combined drug therapy, which in the second stage included clenbuterol. In some patients, the function of the heart was restored to such an extent that the device could be removed.
However, these results did not become the standard of treatment: subsequent studies did not provide unequivocal confirmation, and the contribution of clenbuterol in the combination is difficult to establish. The drug was also studied in neuromuscular diseases, but mostly in small pilot studies.
A review by Lynch and Ryall (2008) concluded that beta-2 agonists have potential for the treatment of muscle wasting, but cardiovascular side effects limit their use, so the search has continued toward more “muscle-selective” molecules.
- Postoperative muscle atrophy—small studies, limited data.
- Heart failure with mechanical support — part of a combined protocol, not a standard.
- Neuromuscular diseases — pilot studies.
Editorial conclusions
Clenbuterol was developed as a long-acting oral bronchodilator for the treatment of asthma and COPD. In some countries, it is still registered for humans, but has given way to inhaled drugs.
The most stable official field of application is veterinary medicine: treatment of obstructive diseases of the respiratory tract in horses and tocolysis in cows. Use as a growth stimulant in livestock is prohibited due to the risk of human poisoning.
Experimental studies in muscle atrophy and heart failure are interesting, but have not turned clenbuterol into an agent with proven benefit in these conditions.
We also advise you to read "Clenbuterol: mechanism of action and effect on the body", "Why Clenbuterol is used in sports: expectations and reality" and "Clenbuterol / Salbutamol" comparison.
References
- Kearns CF, McKeever KH. Clenbuterol and the horse revisited. Vet J. 2009;182(3):384â391.
- Mersmann HJ. Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998;76(1):160â172.
- Birks EJ, Tansley PD, Hardy J, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006;355(18):1873â1884.
- Maltin CA, Delday MI, Watson JS, et al. Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients. Clin Sci (Lond). 1993;84(6):651â654.
- Lynch GS, Ryall JG. Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev. 2008;88(2):729â767.
- Council Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists. Official Journal of the European Communities. 1996.
- Guddat S, FuÃhöller G, Geyer H, et al. Clenbuterol â regional food contamination a possible source for inadvertent doping in sports. Drug Test Anal. 2012;4(6):534â538.
