ADRENERGIC BLOCKING ACTION OF PHENOXYETHYL ANALOGUES OF DIBENAMINE’

Previously reported studies of the structural requirements for activity in the f-haloaikylamine (Dibenamine) series of adrenergic blocking agents demon-strated that the electronic characteristics of aromatic substituents other than benzyl may be suitable to provide activity (Nickerson and Gump, 1949). Among these active substituents the phenoxyethyl grouping is of particular interest. Anan (1929) first demonstrated the adrenergic blocking activity of a number of non-halogenated phenoxyethylamines during a study of possible ergot substitutes which were of interest primarily because they directly stimulated uterine smooth muscle. Subsequent work has confirmed the fact that certain phenoxyethylamines are moderately active in blocking a variety of responses to epinephrine (Levy and Ditz, 1934; Bovet ci al., 1937; Kahane and Levy, 1945; Nickerson, 1949). However, these same compounds possess many undesirable side-effects, including a strong local anesthetic action, direct stimulation of smooth muscle and direct myocardial and central nervous system depression (see Nickerson, 1949). In view of the prolonged and specific action of Dibenamine, it seemed possible tha