title: The beta-adrenoceptor blocking properties of the alpha-methyl analogues of propranolol and practolol in the anaesthetized dog.
abstract: 1. The beta-adrenoceptor blocking properties of alpha-methyl propranolol and alpha-methyl practolol were determined in anaesthetized dogs according to their abilities to modify the isoprenaline-induced effects on diastolic pressure, heart rate, myocardial contractile force, femoral arterial blood flow and pulmonary airway resistance.2. alpha-Methyl propranolol shifted the isoprenaline dose-response curves for the fall in diastolic pressure and the positive inotropic and chronotropic responses to the right in a parallel manner yielding pA(2) and slope values of 6.66 (0.92), 6.34 (0.77) and 6.59 (0.61) respectively. The slopes of the graphs for determining pA(2) values for the cardiac beta-adrenoceptor blocking properties of alpha-methyl propranolol were significantly less than 1 and indicated a mechanism other than simple, competitive, reversible antagonism.3. alpha-Methyl propranolol exerted a much weaker blockade of respiratory smooth muscle beta-adrenoceptors than has been reported for propranolol.4. alpha-Methyl practolol exerted a weaker blocking effect on myocardial beta-adrenoceptors than has been reported for practolol. No significant blockade of vascular or respiratory smooth muscle beta-adrenoceptors occurred after a total cumulative dose of 10 mug/kg of alpha-methyl practolol.5. alpha-Methyl substitution of propranolol and practolol reduces the potency but increases the selectivity of their beta-adrenoceptor blocking properties.6. The beta-adrenoceptors subserving cardiac stimulation, vasodilatation and bronchodilatation are representative of three different beta-adrenoceptor sub-types in the dog.
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D005260:Female; D005263:Femoral Artery; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008745:Methylation; D009130:Muscle, Smooth / Q000187:drug effects; D011217:Practolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D006632:Histamine; D011433:Propranolol; D007545:Isoproterenol; D011217:Practolol