Highlighting the potential neurologic side effects of Beta-Blockers

In addition to their classical mode of action in the brain, circulating factors may modulate the release of reactive oxygen/nitrogen species (ROS/RNS) from endothelial cells that compose the blood-brain-barrier without entering the brain.

Due to their high capacity to diffuse across membranes, ROS/RNS can reach neurons and modify their activity. This study investigates other mechanisms of actions in which beta-blockers may display a central effect without crossing the blood brain barrier (BBB).

Propranolol is the first-line treatment for infants suffering from infantile hemangioma.

Recently, a few authors have raised the question of the potential neurologic side effects of propranolol.

Propranolol is a lipophilic drug and thus has the ability to passively cross the BBB and accumulate into the brain.

Hydrophilic beta-blockers, such as atenolol and nadolol, were therefore introduced in clinical practice. We first performed an oral treatment in mice to measure the accumulation of propranolol, atenolol and nadolol in different brain regions in vivo.

Propranolol is able to cross the BBB and was found in brain tissue in higher amounts than atenolol and nadolol

We then evaluated the ability of these molecules to induce the release of nitric oxide (NO) and hydrogen peroxide (H2O2) ex vivo in the hypothalamus.  However, all of these beta-blockers are able to induce the secretion of signaling molecules (i.e., NO and/or H2O2) in the hypothalamus, independently of their ability to cross the BBB. Our study thus suggests a new potential deleterious impact of hydrophilic beta-blockers in the brain.

Source : Laurens C, Abot A, Delarue A, Knauf C. Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier. Front Neurosci. 2019 Jan 31;13:33. doi: 10.3389/fnins.2019.00033. PMID: 30766473; PMCID: PMC6365417.

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