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Title: L-3,4-(3-3,4-dimethoxyphenethylamino-2-hydroxypropoxy)-phenyl- crotonic acid nitrile.HCl (Hoe 224), a beta-blocking agent with high beta 1-selectivity. Author: Lindner E. Journal: Arzneimittelforschung; 1984; 34(3):270-6. PubMed ID: 6145430. Abstract: L-3,4-(3-3,4-Dimethoxyphene-ethylamino-2-hydroxypropoxy)-phenyl-++ +crotonic acid nitrile X HCl (Hoe 224) has beta 1-blocking action. In the isolated left atrium of the guinea pig, the ED50 necessary to counteract the positive inotropic action of 2 ng/ml isoprenaline (isoproterenol) was determined as 10.3 ng/ml in comparison to the ED50 of propranolol 2.7 ng/ml. On the isolated right atrium of the same animal, the ED50 for inhibition of increased heart rate brought about by 2 ng/ml isoprenaline was 29.5 ng/ml in comparison to the ED50 of propranolol 13.5 ng/ml. On the isolated tracheal chain of the guinea pig 40 micrograms Hoe 224/ml also inhibited relaxation induced by 50 ng isoprenaline/ml only by 31%. The ED50 for propranolol in this experiment was 1.2 ng/ml. Therefore, Hoe 224 is a very specific beta 1-blocker. In the dog anaesthetized with pentobarbital the ED50 of Hoe 224 for depression of dp/dt increase by 0.1 mg isoprenaline/kg i.v. was determined as 85 micrograms/kg i.v. Under the same conditions, the ED50 for propranolol was 10 micrograms/kg i.v., for atenolol 17 micrograms/kg i.v., for practolol 56 micrograms/kg i.v. In the conscious dog, 1.6 mg Hoe 224/kg orally depressed the increase of dp/dt brought about by 0.1 microgram isoprenaline/kg i.v. by 50%. The beta 2-blocking effect of Hoe 224 intraarterially against vasodilating effect of 0.01 microgram isoprenaline/kg given intraarterially in the A. femoralis of anaesthetized dogs was very weak. 100 micrograms Hoe 224/kg reduced the effect of isoprenaline only by 23%, but 2 micrograms propranolol/kg intraarterially reduced this effect by 61%.(ABSTRACT TRUNCATED AT 250 WORDS)[Abstract] [Full Text] [Related] [New Search]