Comparison of beta-ligands used in cattle production: structures, safety, and biological effects

Abstract

Technologies that increase the efficiency and sustainability of food animal production to provide meat for a growing population are necessary and must be used in a manner consistent with good veterinary practices, approved labeled use, and environmental stewardship. Compounds that bind to beta-adrenergic receptors (β-AR), termed beta-adrenergic receptor ligands (β-ligands), are one such technology and have been in use globally for many years. Though all β-ligands share some similarities in structure and function, the significance of their structural and pharmacological differences is sometimes overlooked. Structural variations in these molecules can affect absorption, distribution, metabolism, and excretion as well as cause substantial differences in biological and metabolic effects. Several β-ligands are available for use specifically in cattle production. Ractopamine and zilpaterol are beta-adrenergic agonists approved to increase weight gain, feed efficiency, and carcass leanness in cattle. They both bind to and activate β1- and β2-AR. Lubabegron is a newly developed selective beta-adrenergic modulator with unique structural and functional features. Lubabegron displays antagonistic behavior at the β1- and β2-AR but agonistic behavior at the β3-AR. Lubabegron is approved for use in cattle to reduce ammonia emissions per unit of live or carcass weight. Additionally, lubabegron can withstand prolonged use as the β3-AR lacks structural features needed for desensitization. Due to these unique features of lubabegron, this new β-ligand provides an additional option in cattle production. The individual properties of each β-ligand should be considered when making risk management decisions, as unique properties result in varying human food safety profiles that can determine appropriate safe β-ligand use.

Determination and enantioselective separation of zilpaterol in human urine after mimicking consumption of contaminated meat using high‐performance liquid chromatography with tandem mass spectrometry techniques

“…2 These observations are presumably reason for some β-agonists being used or misused as growth promoters in the farming industry. 1 Representatives of this drug class are clenbuterol, cimaterol, salbutamol, ractopamine, and zilpaterol. Zilpaterol is a synthetic β-adrenoreceptor agonist with an enantiomeric structure (Figure 1).…”

“…Beta-adrenoreceptor agonists (β-agonists) are used as bronchodilators to treat pulmonary diseases in humans and animals. 1 Since the 1980s, various studies have indicated anabolic/growth-promoting effects when β-agonists are used at higher doses, leading to increased muscle mass and reduced body fat percentage. 2 These observations are presumably reason for some β-agonists being used or misused as growth promoters in the farming industry.…”

“…Since the 1980s, various studies have indicated anabolic/growth‐promoting effects when β‐agonists are used at higher doses, leading to increased muscle mass and reduced body fat percentage 2 . These observations are presumably reason for some β‐agonists being used or misused as growth promoters in the farming industry 1 . Representatives of this drug class are clenbuterol, cimaterol, salbutamol, ractopamine, and zilpaterol.…”

Effects of feeding lubabegron on gas emissions, growth performance, and carcass characteristics of beef cattle housed in small-pen environmentally monitored enclosures during the last 3 mo of the finishing period

“…LUB is a selective β-modulator ( SβM ) which selectively binds to the β-adrenergic receptor and has agonistic properties at the β 3 -receptor subtype and antagonistic properties at β 1 - and β 2 -receptor subtypes in cattle ( Dilger et al, 2021 ), and as such, is classified by the Center of Veterinary Medicine ( CVM ) as a ‘beta-adrenergic agonist/antagonist’ ( FDA, 2018 ). This pharmacodynamic profile differentiates LUB from the β-ligands historically used in livestock species, as their apparent mode of action is predominately through agonistic behavior at either the β 1 - or the β 2 -receptor subtype.…”

“…Additionally, LUB selectively binds to β-adrenergic receptors (binding affinity observed at ≤0.5 nM) and has low binding affinity for non-β-adrenergic receptors (i.e., no affinity observed at >300 nM for muscarinic, 5-HT 2 , dopamine D 1 and D 2 , α 1 - and α 2 -adrenergic, benzodiazepine, histamine H 1 , or GABA A receptors; FDA, 2018 ). Because of its selectivity and modulating characteristics, LUB can simply and accurately be described as a selective β-modulator, SβM ( Dilger et al, 2021 ).…”