The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias

Abstract

1 The optical isomers of propranolol have been compared for their β-blocking and antiarrhythmic activities. 2 In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)-propranolol had less than one hundredth the potency of (–)-propranolol. At dose levels of (+)-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram. 3 The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (–)-propranolol. (+)-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose. 4 Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs. 5 The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer. 6 Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (–)-propranolol was 0.09 ± 0.02 mg/kg whereas that of (+)-propranolol was 4.2 ± 1.2 mg/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline. 7 Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (–)-propranolol was significantly smaller than that of (+)-propranolol in both species but much higher than that required to produce evidence of β-blockade. 8 The implications of these results are discussed.