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.
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Selected References
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