Central nervous system effects of beta-adrenergic-blocking drugs: the role of ancillary properties.

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Abstract
Among the side effects commonly reported with the use of .beta.-blockers are symptoms related to the central nervous system (CNS). In this study we compared the effects of four .beta.-blockers with different ancillary properties (atenolol, metoprolol, and propranolol, and pindolol) and placebo on objective and subjective measures of CNS function in 30 healthy male subjects. All subjects were randomly assigned to a double-blind, placebo controlled, Latin-square design study in which five 1 week periods of drug or placebo administration were separated by 2 week washout periods. Laboratory evaluations were conducted at the end of each treatment period, and included multistage exercise stress testing; questionnaire assessments of mood state, sexual function, and sleep habits; tests of psychomotor function; and overnight polysomnographic measures of sleep. Significant effects on sleep continuity were observed for each of the lipophilic drugs, as reflected in the number of awakenings (pindolol = 6.4 .+-. 5.0; propranolol = 6.3 .+-. 3.2; metoprolol = 7.2 .+-. 4.7; atenolol = 3.6 .+-. 2.9; placebo = 3.9 .+-. 2.7) and time of wakefulness (pindolol = 20.6 .+-. 27.- min; propranolol = 15.5 .+-. 23.0 min; metoprolol = 19.5 .+-. 24.3 min; atenolol = 10.2 .+-. 11.6 min; placebo = 9.2 .+-. 74.5 min). Only pindolol significantly affected rapid eye movement (REM) sleep time (pindolol = 54.5 .+-. 21.9 min; placebo = 74.5 .+-. 74.5 min) and REM latency (pindolol = 175.0 .+-. 60.7 min; placebo = 95.4 .+-. 43.8 min). Subjective reports of sleep similarly indicated increased wakefulness and greater restlessness with lipophilic .beta.-blockers. Although higher depression scores were observed in association with pindolol and propranolol, other measures of psychomotor and sexual function failed to show a consistent pattern of results. Exercise stress test results indicated that during exercise all .beta.-blockers depressed heart rate to equivalent degrees. These results provide strong evidence that CNS effects of .beta.-blockers aremodulated by the ancillary properties (e.g., lipophilicity, intrinsic sympathomimetic activity) of the drugs.