A review of the animal pharmacology of labetalol, a combined alpha- and beta-adrenoceptor-blocking drug.

1 The animal pharmacology of labetalol, a drug that blocks both alpha- and beta-adrenoreceptors, is reviewed. 2 In isolated tissues the blockade by labetalol of both alpha- and beta-adrenoreceptors satisfied accepted critera for competitive antagonism. In contrast phentolamine was a competitive antagonist at alpha-adrenoreceptors only, and propranolol a competitive antagonist at beta-adrenoreceptors only. Labetalol was 6-10 times less potent than phentolamine in blocking alpha-adrenoreceptors and 1.5-3 times less potent than propranolol in blocking beta-adrenoreceptors. Labetalol itself was 4-8 times more potent at beta- than at alpha-adrenoreceptors. 3 In anaesthetized dogs labetalol given intravenously blocked vasopressor responses to phenylephrine positive chronotropic, vasodepressor and bronchodilator response to isoprenaline. Phentolamine blocked the effect of phenylephrine only, and propranolol the effects of isoprenaline only. Labetalol was about 7 times less potent than phentolamine in blocking alpha-adrenoreceptors, about 4 times less potent than propranolol in blocking cardiac beta1-adrenoreceptors, and 11-17 times less potent than propranolol in blocking vascular and bronchial beta2-adrenoceptors. This difference in the relative potency of labetalol arises because propranolol is a slightly more potent antagonist at beta2- than at beta1-adrenoreceptors. Labetaol itself was about 16 times more potent at cardiac beta1- than at vascular alpha-adrenoreceptors. In conscious dogs labetaol given orally blocked vasopressor responses to phenylephrine and positive chonotropic responses to isoprenaline. 4 In anesthetized dogs and pithed rats labetaol blocked alpha- or beta-adrenoreceptor-mediated responses to sympathetic nerve stimulation and intravenously administered phenylephrine or isoprenaline to approximately the same extent. 5 Labetalol does not possess partial agonist (intrinsic sympathomimetic) activity at cardiac beta1-adrenoreceptors. 6 The blocking action of labetalol both in vivo was shown to be specific for alpha- and beta-adrenoreceptors. 7 The haemodynamic effects of labetalol are attributable to its adrenoreceptor-blocking actions. The observed responses vary from one experiment situation to another depending on the balance of autonomic influences. For example, in barbitone-anaesthetized dogs, in which sympathetic tone predominates, both labetalol and propranolol reduced heart rate, contractility, output and work--effects which are attributable to beta-adrenoreceptor blockade. Labetalol differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger falls in blood pressure at equipotent beta-adrenoreceptor-blocking doses. These differences are probably attributable to peripheral vasodilatation resulting from the vascular alpha-adrenoreceptor-blocking action of labetalol...