In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.

1In healthy male volunteers after single oral doses, AH 5158 produced inhibition of exercise induced tachycardia, falls in systolic and diastolic pressure at rest and in response to exercise, which are probably related to combined f-and a-adrenoceptor antagonism. 2 At increasing doses from 100 mg to 400 mg there exists a dose related antagonistic effect, though the dominant effect of,-adrenoceptor antagonism is more easily demonstrable than is a antagonism. 3 As indicated by the pattern of pharmacological effects, absorption of the oral drug is good and the duration of action of a 400 mg dose is approximately 8 hours. 4 Despite being administered in j3-adrenoceptor blocking doses, AH 5158 had no adverse effects upon peak expiratory flow at rest or in response to exercise. 5It is concluded that the pharmacological profile of this combined a-and ,B-adrenoceptor antagonism suggests a potential therapeutic role as an antihypertensive drug.

A double‐blind, placebo‐controlled, cross‐over study in 10 healthy male subjects has been carried out to investigate the non‐pulmonary effects of single inhaled doses of salmeterol 100 micrograms, 200 micrograms and 400 micrograms and salbutamol 400 micrograms from a metered‐dose inhaler. At all doses tested, salmeterol produced statistically significant changes in pulse rate, tremor, blood glucose and plasma potassium concentrations, compared with placebo. All changes were dosed related. A number of dose‐related adverse events including tremor, awareness of heart beat and headache were reported after salmeterol administration.

1 The effects of oral propranolol (80 mg), labetalol (400 mg) and placebo on blood pressure, pulse rate and FEV1 at rest and after inhaled histamine, have been compared in six healthy male volunteers. 2 At 90 and 120 min after ingestion propranolol reduced the pulse rate and labetalol reduced the blood pressure, thus confirming absorption of each drug. 3 At 120 min propranolol reduced resting FEV1 and enhanced the fall in FEV1 after histamine, whereas the alterations in FEV1 after labetalol did not differ from placebo. 4 These findings suggest that labetalol is less likely than propranolol to cause bronchoconstriction in asthmatic patients.

1 The potential for tachyphylaxis to the non-pulmonary effects of salmeterol, a longacting selective f32-adrenoceptor agonist was investigated in 12 healthy male subjects in a double-blind two period crossover study design.