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Summary1. 4-Hydroxypropranolol, a metabolite produced after oral administration of propranolol, has been shown to be a /3-adrenoceptor blocking drug. It is of similar potency to propranolol in antagonizing the effects of isoprenaline on heart rate and blood pressure in cats and against isoprenaline protection of guinea-pigs from bronchospasm. It is not cardioselective. 2. In rats depleted of catecholamine 4-hydroxypropranolol produced an increase in heart rate, suggesting that it has intrinsic sympathomimetic activity. 3. In anaesthetized dogs 4-hydroxypropranolol produced a decrease in heart rate and dP/dt and an increase in A-V conduction time at doses within the range 0 09-1 25 mg/kg. These effects are a result of /3-adrenoceptor blockade. In dogs depleted of catecholamines these same doses produced an increase in heart rate and dP/dt and a decrease in A-V conduction time. These responses were antagonized by propranolol, and were due to the intrinsic sympathomimetic activity of the compound. At higher doses (5-25 and 13'25 mg/kg) a further dose dependent decrease in heart rate and dP/dt and an increase in A-V conduction time occurred. This trend was also seen in animals depleted of catecholamines. These changes represent membrane stabilizing activity of 4-hydroxypropranolol.4. 4-Hydroxypropranolol is a potent /8-adrenoceptor blocking drug with both intrinsic sympathomimetic activity and membrane stabilizing activity.

The adrenergic {3-receptor blocking drugs currently undergoing clinical evaluation are classified in relation to their pharmacological properties. Particular consideration is given to those pharmacological properties that may be of importance in the clinical application of these drugs. The present evidence on the role in the {3-blocking action of propranolol in angina pectoris and arrhythmias is reviewed, and it is concluded that this property is of major significance in these indications. Finally, recent advances in this field are summarized and possible future areas for research described.

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The non-stimulant cardioselective beta adrenocepter antagonist atenolol has been studied in volunteers in order to define its pharmacokinetic characteristics. Atenolol (100 and 200 mg orally) is rapidly absorbed, reductions in heart rate and systolic pressure being observed in 30 min. The effect persists for up to 8 h. Over 85% of an intravenous dose is excreted in urine within 24 h but only 50% of an oral dose. The bioavailability of approximately 50% is due to reduced absorption. Peak blood levels are observed at 2-4 h and the half life of atenolol given orally is 5-6 h. Atenolol reduces the cardiac response to standing and head-up tilt. It does not reduce circulating levels of renin but slightly impairs the renin response to tilt. Atenolol both orally and intravenously reduces supine diastolic pressure about four hours after administration, the effect persisting for up to 24 h.