Beta-adrenoceptor blockade and CNS-related subjective symptoms: a randomized, double-blind, placebo-controlled comparison of metoprolol CR/ZOK, atenolol and propranolol LA in healthy subjects.

The effect of once daily treatment with atenolol (100 mg), metoprolol CR/ZOK (100 mg) and propranolol LA (160 mg) for one week on CNS-related subjective symptoms was compared with that of placebo using a randomised, double-blind cross-over design in 12 healthy volunteers. The symptoms were recorded using a previously documented self-administered questionnaire (MSE-profile), which included three dimensions: Contentment, Vitality and Sleep. Compared to placebo, all three beta-adrenoceptor antagonists reduced the exercise heart rate at 24 hours but a somewhat more pronounced effect was found with propranolol LA. No significant difference in any of the dimensions was detected between placebo and either metoprolol CR/ZOK or atenolol tablets. Following propranolol LA treatment a deterioration in the dimensions Vitality and Sleep was observed compared with both placebo and the beta 1-selective drugs. Difference in lipophilicity between the beta 1-selective agents metoprolol and atenolol has little bearing on the occurrence of the CNS-related symptoms, in comparison to the marked effects of the lipophilic and nonselective compound propranolol.