The acute haemodynamic effects of prenalterol, a selective adrenergic beta-1-receptor agonist, were studied in eight healthy male volunteers. Prenalterol was administered i.v. in five increasing doses to a cumulative dose of 5.55 mg. After the last dose of prenalterol, three doses of the selective adrenergic beta-1-receptor antagonist metoprolol were administered i.v. to a cumulative dose of 17.5 mg. After each dose, cardiac output (CO), stroke volume (SV), blood pressure (BP), heart rate (HR), systolic time intervals (STI) and forearm blood flow (FBF) were determined. Prenalterol had the following effects: CO was significantly increased by 21.0% after the fourth dose, but the fifth dose did not further change CO. SV was unchanged after the first four doses, but after the fifth dose a significant decrease in SV of 7.0% was seen. Mean BP was increased significantly by 7.7%, but diastolic BP remained unchanged. HR was increased by 28.4%. Total peripheral resistance was reduced by 8.8%. STI were reduced significantly after the second dose, which indicates that prenalterol has a positive inotropic action. FBF was increased significantly after the fourth dose. After the third dose of metoprolol, the CO, SV, means BP, HR, STI and FBF had returned to their control values. It is concluded that prenalterol has positive inotropic and chronotropic effects on the myocardium, and that metoprolol is a specific antidote.

1 A random double-blind study was performed in healthy volunteers. The immediate effects of three different 3-adrenoceptor blocking agents, metoprolol, pindolol and propranolol, on the plasma concentrations of adrenaline and noradrenaline were compared in a situation of pleasant psychic stimulation during a television-game of tennis. The immediate effects of labetalol in a group of patients with arterial hypertension were studied in a similar experimental situation. 2 During psychic stress the plasma concentration of noradrenaline rose significantly by 85% after placebo, by 95% after labetalol, by 63% after metoprolol and by 55% after propranolol. After pindolol the noradrenaline concentration remained unchanged. 3 During psychic stress the plasma concentration of adrenaline rose significantly by 135% after labetalol, by 110% after metoprolol and by 83% after propranolol. After pindolol and placebo the adrenaline concentration remained unchanged. 4 The present results are taken to indicate that the intrinsic sympathomimetic activity possessed by pindolol prevents the rise in plasma noradrenaline normally seen during psychic stress. It is suggested that P-adrenoceptor blockers with strong intrinsic sympathomimetic effect reduce the release of catecholamines during psychic stress.

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1. The immediate haemodynamic and metabolic effects of intravenous administration of DL-propranolol and D-propranolol were studied in healthy male subjects at rest and during dynamic forearm exercise. The dose of DL-propranolol and of D-propranolol was 0.1 and 1.0 mg/kg body weight respectively. 2. DL-Propranolol reduced heart rate significantly at rest, during forearm exercise and post-exercise, whereas D-propranolol had a lesser effect on heart rate which was significant only at the end of the exercise period. Arterial blood pressure and forearm blood flow were unchanged after either drug. 3. Both drugs reduced the release of lactate from the exercising forearm. Forearm exchange of oxygen, glucose, free fatty acids and triglycerides remained unchanged. 4. The arterial blood glucose concentration increased after D-propranolol, but was unchanged after DL-propranolol. The arterial serum free fatty acid concentration decreased after DL-propranolol, but was not changed after D-propranolol. Arterial concentrations of lactate and triglycerides were not influenced by the drugs. 5. The chronotropic response to beta-adrenoceptor blockade appears to be stereoselective, suggesting specific blockade of beta-adrenoceptors. Metabolic responses to beta-adrenoceptor blockade are difficult to explain in terms of the known adrenoceptor system and may be due to non-specific actions of beta-adrenoceptor antagonists. An exception is inhibition of lipolysis, which is probably mediated via beta-adrenoceptors.