(−)‐Timolol is a more potent antagonist of the positive inotropic effects of (−)‐adrenaline than of those of (−)‐noradrenaline in human atrium

1The affinity of (−)‐timolol for β₁‐ and β₂‐adrenoceptors was determined on isolated atrial preparations from patients undergoing open heart surgery. The times for onset and offset of antagonism of the positive inotropic effects of (−)‐adrenaline and (−)‐noradrenaline by (−)‐timolol were measured.

2The antagonism of the positive inotropic effects of (−)‐adrenaline and (−)‐noradrenaline by (−)‐timolol (0.1–100 nm) was simple competitive in human atrium tissue. The slope of Schild‐plots was not significantly different from 1.0 [0.93±0.09 for (−)‐adrenaline, 0.97±0.09 for (−)‐noradrenaline].

3The inotropic effects of (−)‐adrenaline were antagonized significantly more by each concentration of (−)‐timolol than those of (−)‐noradrenaline. K_B‐values (‐log m) were 10.10±0.09 against (−)‐adrenaline and 9.43±0.07 against (−)‐noradrenaline (P<0.001).

4Blocking kinetics of (−)‐timolol for the β‐adrenoceptor were relatively slow. Half‐times for the onset of blockade by 10 times K_B of (−)‐timolol were approximately 30 min for both (−)‐adrenaline and (−)‐noradrenaline; offset times were similar.

5It is concluded that (−)‐timolol has a higher affinity for the β₂‐adrenoceptor than for the β₁‐adrenoceptor in human atrium. This property may be beneficial clinically in protecting against the β₂‐adrenoceptor hypersensitivity induced by cardiac β₁‐adrenoceptor blockade, but also explain why severe asthma can occur after administration of very low intra‐ocular doses of the drug.

DOI: 10.1046/j.1365-2125.1996.39412.x

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