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

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Abstract
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 beta1‐selective drugs.Difference in lipophilicity between the beta1‐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.