Activity of N-(Phenethyl)phenylethanolamines at β[sub 1] and β[sub 2] Adrenoceptors: Structural Modifications Can Result in Selectivity for Either Subtype.

A series of phenylethanolamines bearing a 2-[1-phenylpropyl] substituent on the nitrogen atom was evaluated in vitro for activity at β[sub 1] - and β[sub 2] -adrenoceptors. As previously observed, the presence of 3,4-dihydroxy substitution on phenylethanolamine is required for potent activation of both subtypes, whereas the 3,5-dihydroxy analog showed selectivity for the β[sub 2] -subtype. Replacement by a carboxyl group of the 4-hydroxyl group on the aralkyl nitrogen substituent produced only a small reduction in β[sub 1] potency (5-fold), whereas β[sub 2] potency was reduced by more than 100-fold. Hence this structural class includes agonists having either a β[sub 1] , nonselective β[sub 1] /β[sub 2] or β[sub 2] selectivity profile.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]