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Influence of changes in amine substitution on the β‐adrenoceptor stimulant activity of soterenol and related compounds in the anaesthetized cat
Author(s) -
Malta E.,
Raper C.
Publication year - 1975
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1975.tb01843.x
Subject(s) - isoprenaline , chemistry , isopropyl , potency , amine gas treating , medicinal chemistry , contractility , stereochemistry , propranolol , medicine , stimulation , biochemistry , in vitro , organic chemistry
SUMMARY 1. Three 3‐methanesulphonamido, 4‐hydroxy ring substituted phenylethanol‐amines with n ‐isopropyl (soterenol), n ‐ t ‐butyl (MJ7999–1) and n ‐(1‐phenyl‐ t ‐butyl) (MJ9184–1) amine substituents have been compared with (—)‐isoprenaline for their ability to produce β‐receptor mediated reductions in serotonin‐induced increases in pulmonary resistance, decreases in soleus muscle contractility, and increases in heart rate in anaesthetized cats. For each parameter, the dose of a compound required to produce 50% of its maximal response (ED 50 ) was calculated. 2. For all three parameters (—)‐isoprenaline was the most potent of the compounds studied, and the rank order of potency of the methanesulphonanilides was MJ9184–1 ( n ‐(1‐phenyl‐ t ‐butyl))≃MJ7999–1 ( n ‐ t ‐butyl)> soterenol (N‐isopropyl). 3. For each individual drug, molar dose‐ratios [drug: (—)‐isoprenaline] were calculated. Ratios for the effects of the compounds on the soleus muscle and in the bronchi were similar. With each compound higher dose‐ratios were found in the heart. The rank order for relative β 2 ‐selectivity was soterenol ( n ‐isopropyl)> MJ7999–1 ( n ‐ t ‐butyl)≃MJ9184–1 ( n ‐(1‐phenyl‐ t ‐butyl)).