Influence of changes in amine substitution on the beta-adrenoceptor stimulant activity of soterenol and related compounds in the anaesthetized cat.
1. Three 3-methanesulphonamido, 4-hydroxy ring substituted phenylethanolamines 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 beta-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 (ED50) 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))congruent to MJ7999-1 (N-t-butyl) greater than 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 beta2-selectivity was soterenol (N-isopropyl) greater than MJ7999-1 (N-t-butyl) congruent to MJ9184-1 (N-(1-phenyl-t-butyl)).
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004983:Ethanolamines / Q000031:analogs & derivatives / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
D000318:Adrenergic beta-Agonists; D000588:Amines; D004983:Ethanolamines; D012701:Serotonin; D011433:Propranolol; D007545:Isoproterenol