Interaction studies and other investigations of the pharmacology of propofol ('Diprivan').

The anaesthetic properties of propofol ('Diprivan') have been described previously. This report summarizes additional studies designed to investigate some aspects of the general pharmacology of propofol. Following recovery from anaesthesia with propofol there was no evidence of any central anticholinergic or anticonvulsant effect in mice. An anti-convulsant effect followed thiopentone anaesthesia. In mice anaesthetized with propofol 24 h after the last of 4 daily doses of phenelzine, amitriptyline, diazepam or alcohol, no marked potentiation of anaesthesia was found. Pretreatment with alcohol on the day of anaesthesia potentiated thiopentone but not propofol anaesthesia. Oral doses of propofol up to 300 mg/kg failed to induce anaesthesia in mice. The acute administration of the beta-adrenoceptor antagonists, atenolol or propranolol was well tolerated during anaesthesia with propofol in pigs. In the cat the arrhythmia threshold to adrenaline was greater than that in cats anaesthetized with halothane and no ganglion blocking or alpha-adrenoceptor antagonist properties were demonstrated. No potent or specific agonist or antagonist properties were detected in the range of in vitro systems examined. Neither propofol nor thiopentone had any effect on ADP-induced platelet aggregation or whole blood clotting time. Bronchomotor tone and gastrointestinal motility were unaffected by propofol. Tests of renal function indicated only a slight reduction in sodium excretion, similar to that seen with thiopentone. A normal corticosterone response to ACTH was seen in rats anaesthetized for 90 min with an infusion of propofol.