[Pharmacology of 1-phenylaminoethylamino-3-(phenoxy)propanol derivatives with beta-adrenergic action]

In the framework of a screening test of new phenoxyalkanolamines the authors tested derivatives with the basic structure Ph1--NHCH2CH2NHCH2CH(OH)CH2--OPh2 for beta-adrenergic blocking activity and sympathicomimetic action on the spontaneously beating atrial preparation from the guinea-pig and on the circulation of the cat. Derivatives with the substituents 2,5-dimethyl, 2-nitro, 3-nitro, 2,6-dimethyl and 2-chloro at Ph1 produced in the atrial preparation a some 3- to 10fold stronger beta 1-adrenergic blockade than propranolol. In in vivo experiments on the cat, all of these compounds had a potent sympathicomimetic effect on the heart, so that they may be classified as specific beta-adrenergic antagonists. The addition of 4-nitro, 3-methyl and 4-ureido at Ph2 reduces the beta-adrenergic blockade and suppresses the sympathicomimetic action. 1-(3',4'-Dimethoxyphenylethylamino)-2-hydroxy-3-phenoxypropane and its derivates showed a similar behaviour as described by Hoefle [8]. 1-[beta-(3-Nitrophenylamino)ethylamino]-2-hydroxy-3-phenoxypropane hydrochloride exhibited a particularly strong and long-lasting sympathicomimetic effect. Studies on the dog revealed a specific beta 1-mimetic action; in the effective dose range of 10-30 micrograms/kg i.v., a positive inotropic effect prevailed, and the effect on heart rate was but small. No beta-adrenergic blockade or mimetic action on the peripheral vascular system was observed.