The “inactive metabolite approach” was used to design a series of “soft” drugs derived from the acidic metabolite of metoprolol. Pharmacokinetic and pharmacodynamic properties of these novel “soft” 0-adrenoceptor antagonists were determined: half-lives in human blood ranged from 5 to 754 min. The rates of in vivo disappearance of representative slow, medium, and fast hydrolyzing esters were determined in rats. In each case rapid and ...