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Home » Hormones » PHARMACOLOGY » Phenethanolamine β-adrenoceptor agonists

Friday, January 18, 2013

Phenethanolamine β-adrenoceptor agonists

Phenethanolamine β-adrenoceptor agonists (βAA) 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 βAA 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, β2 receptors in tracheal and skeletal muscle, and β3 receptors in brown adipose tissue. In general, βAA 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. β-Adrenergic agonist use leads to an increase in muscle mass caused by increased protein synthesis with a concomitant decrease in protein degradation, 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 selected βAA. The physiologic activity of βAA depends on the dose, receptor binding specificity, mode of adminstration, rate of absorption, and metabolic clearance rate in treated animals.
The major use of βAA in food animal production is to increase carcass leanness. 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.
Side effects depend on compound administered, dose used, and species treated, but those selected for commercial use have minimal side 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 increase toughness of meat in cattle. Due to potential side effects and adverse effects on meat quality, many compounds are unlikely to be approved for use as growth promotants, although some countries do allow the use of specific compounds in pig production (ractopamine). The use of β-agonists as growth promoters is banned in the EU. Illegal use of clenbuterol in cattle and certain βAA 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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