Brain levels and acute antihypertensive activity of beta-blockers

The penetration of beta-adrenoceptor blockers into the cerebrospinal fluid and into brain tissue is related to the lipophilicity of these drugs, as reflected by the partition coefficients between octanol and aqueous buffers. However, experimental techniques in animal models show no obvious relationships between the degree of brain penetration and the acute central antihypertensive effect of certain beta-blockers. This discrepancy is demonstrated convincingly by comparative experiments with atenolol and metoprolol. Both drugs are beta 1-selective blockers, and atenolol is highly polar, whereas metoprolol is lipophilic. Both these beta-blockers penetrate the CNS but to differing degrees. The experiments performed with these compounds support other studies described in the literature and do not suggest that there is a central mechanism which underlies the antihypertensive activity of beta-blockers.