Central nervous system side effects of beta-adrenergic blocking agents with high and low lipid solubility

beta-adrenergic blocking agents have undesirable effects believed to be mediated through the central nervous system (CNS). If these effects are due to direct CNS action, less lipid soluble agents ought to have fewer effects. Accordingly, several formal psychological tests of items such as mood, motivation, and anxiety were used in a double-blinded crossover study in 17 hypertensive subjects taking equipotent beta blocking agents with high (propranolol) and low (atenolol) lipid solubility. Patients had less negative effects (p less than 0.05) on 12 of 21 items evaluated with atenolol compared to propranolol while peripheral beta blockade [beta 1, exercise heart rate (HR), and blood pressure (BP)] was equivalent. These results suggest that the mental changes which accompany beta blockade therapy are mediated directly in the CNS and that less soluble drugs can be expected to have fewer CNS effects.