Species difference in the beta1/beta2-adrenoceptor selectivity of SM220CL in the cat and guinea-pig.
The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability to increase the heart rate (beta1), reduce serotonin-induced increases in pulmonary resistance (beta2), and decrease soleus muscle contractility (beta2) in vivo in the two species. 3. In all experiments cumulative concentration or dose-effect curves were established, EC50 or ED50 values obtained and molar activity-ratios (Sm220Cl: (-)-isoprenaline) calculated. 4. Calculated selectivity ratios [activity-ratio (heart):activity-ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed beta2-receptor selectivity. This was more marked in guinea-pig than in cat preparations. 5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non-selective in its actions for beta1- and beta2-receptor mediated responses, while marked beta2-receptor selectivity was obtained in the guinea-pig. 6. Since in both species the activity-ratios for beta2-receptor mediated actions are similar, the differences in the beta1/beta2-receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013045:Species Specificity; D013997:Time Factors; D014132:Trachea / Q000187:drug effects
D002395:Catecholamines; D004983:Ethanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C014914:N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine; D006632:Histamine; D002217:Carbachol; D007545:Isoproterenol