Pafenolol, a highly selective ?1-adrenoceptor–antagonist, in asthmatic patients: Interaction with terbutaline

Abstract

Pafenolol, a new β1‐adrenoceptor antagonist, has been shown in animals to be more selective for β1‐adrenoceptors than metoprolol. It was studied in asthmatic patients to evaluate whether it was more selective with respect to circulatory effects and especially whether this selectivity influenced bronchial muscle tone less than metoprolol, which has been shown to have β1‐adrenoceptor selectivity similar to that of atenolol. Intravenous pafenolol (5 mg and 7.5 mg), metoprolol (15 mg), and saline were given double‐blind at random and thereafter four increasing doses of terbutaline were given intravenously to seven asthmatic patients with reproducible reversibility of airways obstruction. After the terbutaline dose‐respone curve was determined, terbutaline was inhaled three times in increasing doses. A separately reported exercise study in the same patients showed that 5 mg pafenolol and 15 mg metoprolol were equipotent with respect to β1‐adrenoceptor blockade, whereas 7.5 mg pafenolol tended to increase the blockade. The reflex tachycardia on terbutaline stimulation after pafenolol was greater than after metoprolol due to less blockade of β2‐adrenoceptors in peripheral blood vessels. The bronchial effect of pafenolol was equal to that of saline, but there was a difference between the terbutaline dose‐response curves after pafenolol and metoprolol that caused a rightward shift of the dose‐response curve. Thus, pafenolol was shown to be more β1‐selective than metoprolol.