Selectivity of beta-adrenoceptor agonists and antagonists on bronchial, skeletal, vascular and cardiac muscle in the anaesthetized cat.
1 The potencies of fifteen beta-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The beta-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 mug/kg and maximal or near maximal responses were produced by 0.3-1 mug/kg. Trimetoquinol was also an essentially unselective agonist. 3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist - AH 7616 (4-hydroxy-alpha1-[[(1-methyl-3,3-diphenyl-propyl)amino]-methyl]-m-xylene-alpha1, alpha3-diol, acetate) - was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its beta-adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The beta-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of beta-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual beta-adrenoceptor sub-classification.
Selectivity of beta-adrenoceptor agonists and antagonists on bronchial, skeletal, vascular and cardiac muscle in the anaesthetized cat. 1 The potencies of fifteen beta-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The beta-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 mug/kg and maximal or near maximal responses were produced by 0.3-1 mug/kg. Trimetoquinol was also an essentially unselective agonist. 3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist - AH 7616 (4-hydroxy-alpha1-[[(1-methyl-3,3-diphenyl-propyl)amino]-methyl]-m-xylene-alpha1, alpha3-diol, acetate) - was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its beta-adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The beta-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of beta-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual beta-adrenoceptor sub-classification.