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SELECTIVITY OF β‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON BRONCHIAL, SKELETAL, VASCULAR AND CARDIAC MUSCLE IN THE ANAESTHETIZED CAT
Author(s) -
APPERLEY G.H.,
DALY M.J.,
LEVY G.P.
Publication year - 1976
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1976.tb07473.x
Subject(s) - practolol , isoprenaline , agonist , endocrinology , medicine , chemistry , potency , propranolol , blood pressure , cardiac muscle , soleus muscle , skeletal muscle , bronchospasm , pharmacology , receptor , stimulation , biochemistry , asthma , in vitro
1 The potencies of fifteen β‐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 β‐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 μg/kg and maximal or near maximal responses were produced by 0.3‐1 μg/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‐α 1 ‐[[(1‐methyl‐3,3‐diphenyl‐propyl)amino]methyl]‐m‐xylene‐α 1 ,α 3 ‐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 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 β‐adrenoceptor agonist action. 5 The fifteen test agonists were longer acting than (—)‐isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The β‐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 tremor‐enhancing properties of β‐adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual β‐adrenoceptor sub‐classification.