Comparison of the effects of (--)-isoprenaline, orciprenaline terbutaline, and Me506 on heart rate, soleus muscle contractility and pulmonary resistance of anaesthetized cats.
1. Three resorcinol derivatives with N-isopropyl (orciprenaline), N-t-butyl (terbutaline) and N-p-hydroxypheny-t-butyl (Me506) 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. 2. For all parameters studied the four compounds produced similar maximal responses and dose-response curves were close to parallel. From the graphs doses of the compounds producing 50% of the maximal response (ED50) were interpolated, and from these dose-ratios with respect to (--)-isoprenaline [drug ED50:(--)-isoprenaline ED50] were calculated on a molar basis. 3. Increasing the size of the amine substituent from N-isopropyl to N-t-butyl led to an increase in beta-receptor stimulant activity in bronchial and skeletal muscle, but not in the heart. The change from N-t-butyl to N-p-hydroxyphenyl-t-butyl did not further affect stimulant activity in any of the parameters studied. 4. Calculation of selectivity ratios [molar dose-ratio (heart): molar dose-ratio (pulmonary resistance)] showed that orciprenaline was non-selective, and that terbutaline and Me506 showed a similar degree of selectivity for beta2- as opposed to beta1-receptor mediated actions.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D012118:Resorcinols / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013726:Terbutaline / Q000494:pharmacology*
D002082:Butylamines; D012118:Resorcinols; D009921:Metaproterenol; D007545:Isoproterenol; D013726:Terbutaline