The β‐adrenoceptor blocking properties of the α‐methyl analogues of propranolol and practolol in the anaesthetized dog

Summary1 The β‐adrenoceptor blocking properties of α‐methyl propranolol and α‐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 α‐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 β‐adrenoceptor blocking properties of α‐methyl propranolol were significantly less than 1 and indicated a mechanism other than simple, competitive, reversible antagonism. 3 α‐Methyl propranolol exerted a much weaker blockade of respiratory smooth muscle β‐adrenoceptors than has been reported for propranolol. 4 α‐Methyl practolol exerted a weaker blocking effect on myocardial β‐adrenoceptors than has been reported for practolol. No significant blockade of vascular or respiratory smooth muscle β‐adrenoceptors occurred after a total cumulative dose of 10 μg/kg of α‐methyl practolol. 5 α‐Methyl substitution of propranolol and practolol reduces the potency but increases the selectivity of their β‐adrenoceptor blocking properties. 6 The β‐adrenoceptors subserving cardiac stimulation, vasodilatation and bronchodilatation are representative of three different β‐adrenoceptor sub‐types in the dog.