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CNS-related (side-)effects of β-Blockers with special reference to mechanisms of action

  • β-Blockers And CNS Side-Effects
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Summary

β-Adrenoreceptor antagonists are liable to produce behavioural side-effects such as drowsiness, fatigue, lethargy, sleep disorders, nightmares, depressive moods, and hallucinations. These undesirable actions indicate that β-Blockers affect not only peripheral autonomic activity but also some central nervous mechanisms. In experimental animals β-Blockers have been found to reduce spontaneous motor activity, to counteract isolation-, lesion-, stimulation-and amphetamine-induced hyperactivity, and to produce slow-wave and paradoxical sleep disturbances. Furthermore, central effects such as tranquillizing influences are used for the treatment of conditions such as anxiety. Several different mechanisms of action could be responsible for these CNS effects: (1) Centrally mediated specific actions on centrally located β-adrenergic receptors, known to exist downstream from, and at the terminals of, ‘vigilance-enhancing’ central noradrenergic pathways. (2) Centrally mediated specific actions on centrally located receptors of the non-adrenergic type; an affinity of some β-Blockers towards 5-HT-receptors is well documented. (3) Centrally mediated non-specific actions on centrally located neurones, owing to the membrane-stabilizing effects of β-Blockers. (4) Peripherally mediated actions whereby β-Blockers induce changes in the autonomic activity in the periphery, which are relayed to the CNS to induce changes in activity of a variety of central systems. It can be assumed that with any one of the β-Blockers all these mechanisms come into play, yet with varying degrees depending on characteristics of the drugs such as lipophilicity and hydrophilicity, the ratio of antagonist versus (partial) agonist properties, affinity to ‘alien’ receptor sites, strength of membrane-stabilizing activity, stereospecific affinity, and potency.

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    W. P. Koella

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Koella, W.P. CNS-related (side-)effects of β-Blockers with special reference to mechanisms of action. Eur J Clin Pharmacol 28 (Suppl 1), 55–63 (1985). https://doi.org/10.1007/BF00543711

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