Pharmacological effects of labetalol in man.

1 The pharmacological effects of labetalol have been studied in normal healthy subjects. The results of these studies are reviewed. 2 In the evaluation of the beta-adrenoreceptor-blocking effects of labetalol various indices of beta-adrenoceptor blockade in man were used. Labetalol administered orally and intravenously competitively antagonized the effects of isoprenaline on heart rate and diastolic blood pressure. The beta-adrenoceptor blockade induced was regarded as 'non-selective'. In addition, labetalol produced dose-related inhibitory effects on exercise-induced increases in heart rate any systolic blood pressure and similar dose-related inhibitory effects on the tachycardia induced by valsalva's manoeuvre. Labetalol had only a modest inhibitory effect on the tachycardia induced by tilting since blood pressure was reduced on a dose-related basis. 3 Labetalol was a specific competitive antagonist of the alpha-adrenoceptor agonist effects of systemically administered phenylephrine and locally infused noradrenaline. In addition, oral and intravenous administration of labetalol reduced systolic and diastolic blood pressure in the supine, standing and sitting positions. 4 The onset and duration of the alpha- and beta-antagonist effects of oral labetalol did not seem to be dissociated in time and there was a close correlation between the change in plasma concentration and pharmacological effects. 5 In comparative studies with propranolol, similar beta-antagonist effects were observed but propranolol was 4-6 times more potent weight for weight. Precise comparison, however, was complicated by the combined alpha- and beta -effects of labetalol, especially as the predominant effect of labetalol in normotensive subjects was to reduce blood pressure; whereas the predominant effect of propranolol was to reduce heart rate. In addition propranolol had inhibitory effects on ventilatory function in normal subjects, whereas labetalol in equivalent beta-adrenoreceptor-blocking doses did not. 6 From the details of the studies reviewed it was concluded that in man labetalol possesses combined alpha- and beta-adrenoreceptor antagonist properties.