Summary
The longissimus dorsi muscles of cattle are highly responsive to the anabolic effects of ß2-adrenoceptor agonists, and in the present study were shown to be ß1- rich and homogeneous source of ß2-adrenoceptors.
Structural analogues of the ß2-adrenoceptor agonist clenbuterol were prepared in order to examine the relative importance of the benzylic hydroxyl functionality and the aromatic ring halogen substituents in determining the affinity of phenylethanolamines for ß2-adrenoceptors in bovine muscle. It was calculated that the hydroxyl-hydrogen bonding interaction of these compounds contributes only 1–2 kcal/mol to the total binding energy. The aromatic halosubstituents contributed up to 3 kcal/mol to the total binding energy, and we suggest that the relative importance of the latter functionality has been previously underestimated.
There was ß1- poor correlation between the affinity of clenbuterol analogues for binding to ß2-adrenoceptors, and the potency of these compounds in reducing urinary nitrogen excretion after oral administration to female rats. We suggest that ß2-drenoceptor agonist efficacy is reduced in phenylethanolamine compounds when iodine is present on the aromatic ring. In contrast, the increased potency of a ketone derivative might be explained by conversion in vivo to clenbuterol, with increased bioavailability of this ß2-agonist at the site of action.
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Sillence, M.N., Pegg, G.G. & Lindsay, D.B. Affinity of clenbuterol analogues for ß2-adrenoceptors in bovine skeletal muscle and the effect of these compounds on urinary nitrogen excretion in female rats. Naunyn-Schmiedeberg's Arch Pharmacol 344, 442–448 (1991). https://doi.org/10.1007/BF00172584
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DOI: https://doi.org/10.1007/BF00172584