Blocking of inhibitory adrenergic receptors by a dichloro analog of isoproterenol.

1-(3949 Dichlorophenyl)-2-isopropylaminoethanol hydrochloride (20522), the dichloro analog of isoproterenol, selectively blocked some inhibitory effects of epinephrine and isoproterenol. The depressor action of isoproterenol and the secondary depressor action of epinephrine were inhibited by the dichloro analog which of itself had at most caused a transient fall in blood pressure. The inhibitory effect of epinephrine on isolated rabbit intestine was blocked by 20522. On rat uterus, however, 20522 failed to block epinephrine relaxation except with doses in which the analog itself caused considerable decrease in tone. The dichloro analog caused only slight decrease of intrapulmonary resistance to air flow in the ergotoxine-treated decerebrate-pithed dog, but had no action on pilocarpine bronchoconstriction. The administration of 20522 blocked the usual epinephrine or isoproterenol release of this bronchoconstriction. On isolated guinea pig tracheal chain, 20522 inhibited epinephrine and isoproterenol relaxation of pilocarpine-induced spasm. This action appeared to be competitive since large doses of epinephrine could partially overcome the blocking action of 20522. Further, 20522 was washed off only with difficulty, suggesting a rather tight drug-receptor complex. It seemed probable that 20522 was combining with certain adrenergic inhibitory receptor without itself causing much physiological effect., and yet was competing for these sites with physiologically active amines.