COGNITIVE EFFECTS OF BETA-ADRENERGIC ANTAGONISTS AFTER SINGLE DOSES -PHARMACOKINETICS AND PHARMACODYNAMICS OF PROPRANOLOL, ATENOLOL, LORAZEPAM, AND PLACEBO

The behavioral effects of two beta-adrenergic receptor antagonists, se lected to represent differing lipophilicity, were evaluated in a doubl e-blind, single-dose, parallel-group study. A group of 55 healthy volu nteers (mean age, 28 years) received single oral doses of placebo, ate nolol (50 mg), propranolol (40 mg), or lorazepam (2 mg). Plasma drug c oncentrations, self-ratings of sedation and mood, observer ratings of sedation, and performance on the Digit Symbol Substitution Test (DSST) were assessed at multiple times during 24 hours after drug administra tion. Information acquisition and recall were tested at 3 and 24 hours after drug administration. Lorazepam significantly increased sedation and fatigue, impaired DSST performance, and impaired memory. The time course of these changes was highly consistent with plasma lorazepam c oncentrations. In contrast, atenolol and propranolol produced at most small changes in self-ratings and observer ratings and did not alter D SST performance or memory. Under experimental conditions that are sens itive to the depressant effects of a typical benzodiazepine, single do ses of atenolol and propranolol produced no meaningful changes, compar ed with placebo.