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β-Adrenergic Agonists


Christopher D. Reinhardt

, BS, MS, PhD, Animal Sciences and Industry, Kansas State University

Last full review/revision Dec 2013 | Content last modified Jun 2016

As of 2015, there are two β-adrenergic agonists (βAAs) approved for use as growth promotants in feedlot cattle in the USA: ractopamine and zilpaterol. Phenethanolamine βAAs are chemically similar in structure to epinephrine and norepinephrine and have paracrine, neurotransmitter, and endocrine (hormonal) effects. There is a range of βAA compounds resulting from structural modifications and aromatic ring substitution. The βAAs bind to β-adrenergic receptors, which have been classified into β1, β2, and β3 subtypes based on the physiologic response obtained. β1 receptors are located primarily in cardiac muscle but also can be found in skeletal muscle, β2 receptors in tracheal and skeletal muscle, and β3 receptors in brown adipose tissue. In general, βAAs have specificity for receptor subtypes, thereby providing specificity regarding their physiologic actions. However, there are multiple receptor subclasses in most tissues, and the relative concentrations of β1 and β2 receptors in a tissue determine the physiologic response. Muscle and adipose cells have predominantly β2 receptors. βAA use leads to an increase in muscle mass caused by upregulation of mRNA transcription, resulting in increased protein synthesis, and a decrease in carcass fat due to decreased rates of lipid accretion. The exact proportion of receptor subtypes varies between tissues and also across species, resulting in species-specific responses to select βAAs. For example, swine are believed to have more β1 than β2 receptors in their skeletal muscle; ruminants are believed to have more β2 than β1 receptors. The physiologic activity of βAAs depends on the dose, receptor binding specificity, mode of administration, rate of absorption, and metabolic clearance rate in treated animals. Also, because tissue becomes refractory to exogenous βAA administration, βAAs are fed only during the final days of the finishing phase; extended feeding ultimately results in a complete loss of tissue response to βAAs.

The major use of βAAs in food animal production is to increase carcass leanness and lean tissue produced per animal. In cattle and sheep, weight gain, gain:feed ratio, and meat content are increased by 10%–20% and lipid content is decreased by 7%–20%. In swine and chickens, responses are much lower, with pigs responding better than chickens. Weight gain is increased by 2%–4%, and gain:feed ratio is slightly improved in chickens but not in pigs. Meat content is increased by 2%–4% and lipid content decreased by 7%–8% in chickens and pigs.

Adverse effects depend on compound administered, dose used, and species treated, but those selected for commercial use have minimal adverse effects. They are orally active. Dosage level of the compound used affects the response obtained; the optimal dose often varies for different production variables measured. The most consistent effects are increased proportion of lean meat, but the effects on meat quality vary with compound used, dosage given, duration of treatment, and species treated. Certain compounds have been reported to decrease tenderness of meat in cattle. The use of β-agonists as growth promoters is banned in the EU. Illegal use of clenbuterol in cattle and certain βAAs in poultry is a threat in some countries, requiring vigilance by regulatory authorities. The longterm accumulation of these compounds in hair and ocular tissue has been used to screen for their presence in some countries.

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There are many anthelmintics but most come from only three classes of compounds that act in similar ways. Which class of compounds is NOT one of the main three?
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