SummaryIntravenous infusions of phenylephrine, noradrenaiine, adrenaline, and isoprenaline were given to healthy human volunteers after five to seven days on phenelzine, tranylcypromine, or imipramine, and cardiovascular responses were compared with those observed under control conditions. With monoamine oxidase inhibitors there was a 2-2k fold potentiation of the pressor effect of phenylephrine, but no clinically significant potentiation of cardiovascular effects of noradrenaline, adrenaline, or isoprenaline. With imipramine there was potentiation of the pressor effects ofphenylephrine (2-3 fold), noradrenaline (4-8 fold), and adrenaline (2-4 fold); there were dysrhythmias during adrenaline infusions, but no noticeable or consistent changes in response to isoprenaline.Noradrenaline and adrenaline in amounts contained in local anaesthetics used in dentistry are not likely to be significantly potentiated in otherwise healthy patients receiving monoamine oxidase inhibitors. Hazardous potentiation of their cardiovascular effects might occur in patients receiving tricyclic antidepressants.Our observations do not indicate that the hazards associated with isoprenaline inhalation by bronchial

1.Intravenous administration of compound AH 51 58, which possesses alpha-and beta-adrenergic receptor-blocking properties, produces haemodynamic effects similar to those seen from the combined effects of propranolol and hydrallazine.2. Chronic oral administration has demonstrated that compound AH 5158 is an effective hypotensive agent capable of controlling the blood pressure in patients previously requiring large doses of drugs such as methyldopa. Some postural and exercise hypotension may be seen with larger doses.

Labetalol 1.5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure.Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1: 7, whereas in the same subjects after oral labetalol the ratio was approximately 1: 3 as previously reported.Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1: 6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1 :3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol.Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect.Labetalol is a compound possessing combined alpha and beta adrenoceptor antagonist properties (Farmer et al., 1972). Consequently it has been assessed in clinical practice as an antihypertensive agent. Prichard et al. (1975) and Koch (1976)

1 Thirty-two hypertensive patients have been treated with labetalol for periods of up to 7 years. 2 Ten patients observed for 6 years from the time of stabilization of dosage, did not show any tolerance to labetalol. 3 Postural and exercise hypotension were not seen in these patients over this prolonged follow-up, although they were seen in other patients given over 2 g labetalol daily.

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