Effect of fluorine substitution on the agonist specificity of norepinephrine

Substitution of fluorine for hydrogen in position 2, 5, or 6 of the aromatic ring of norepinephrine markedly alters the alpha- and beta-adrenergic agonist properties of norephinephrine. The 6-fluoro isomer is an beta-adrenergic agonist with virtually no beta agonist activity, while the 2-fluoro isomer is a beta-adrenergic agonist with little alpha activity. The 5-fluoro isomer is equipotent with norepinephrine as an alpha agonist and significantly more potent as a beta agonist. The possible physiochemical basis for these differences is discussed.