The cardioselectivity of β‐adrenergic blocking agents revealed by interaction with salbutamol and isoproterenol in the KCN test in rats

The interaction of seven β‐adrenergic blocking agents with salbutamol and isoproterenol was studied in the potassium cyanide test in rats. Salbutamol was used at a dose that provided protection from KCN lethality and isoproterenol at an overdose that failed to protect, presumably because of latent cardiotoxicity. Salbutamol‐induced protection was abolished at the following doses (s.c., mg/kg): timolol (0.0085), bunolol (0.010), propranolol (0.038), pindolol (0.15), metoprolol (3.93), atenolol (5.69), and practolol (> 10.0). Survival was restored dose‐dependently in isoproterenol‐overdosed rats only by atenolol (0.44), practolol (0.51) and metoprolol (1.06). The cardioselectivity ratio (i.e., salbutamol antagonism/isoproterenol antagonism) for these three compounds was as follows: practolol (> 19.6), atenolol (12.9), and metoprolol (3.82). The described interaction tests appear to provide experimental data that are useful for the evaluation of cardioselective β‐adrenergic blockade.