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

Abstract

1 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 pA₂ 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 pA₂ 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.