Cognitive effects of β-adrenergic antagonists after single doses: Pharmacokinetics and pharmacodynamics of propranolol, atenolol, lorazepam, and placebo

Abstract

The behavioral effects of two beta-adrenergic receptor antagonists, selected to represent differing lipophilicity, were evaluated in a double-blind, single-dose, parallel-group study. A group of 55 healthy volunteers (mean age, 28 years) received single oral doses of placebo, atenolol (50 mg), propranolol (40 mg), or lorazepam (2 mg). Plasma drug concentrations, 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 administration. 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 concentrations. In contrast, atenolol and propranolol produced at most small changes in self-ratings and observer ratings and did not alter DSST performance or memory. Under experimental conditions that are sensitive to the depressant effects of a typical benzodiazepine, single doses of atenolol and propranolol produced no meaningful changes, compared with placebo.