Premium
Why are non‐sedating antihistamines non‐sedating?
Author(s) -
Timmerman H.
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00003.x-i1
Subject(s) - lipophilicity , extravasation , blood–brain barrier , histamine , antihistamine , chemistry , pharmacology , receptor , histamine h1 receptor , histamine receptor , histamine antagonists , stereochemistry , medicine , immunology , biochemistry , central nervous system , antagonist
In this paper several factors which may influence the potential of a certain antihistamine to cause CNS‐related side‐effects are discussed. It is shown by pharmacological studies that the H 1 receptors occurring in CNS tissue or in peripheral organs do not differ with regard to their affinity for H 1 blockers. There is also no other evidence for subtypes of the H 1 receptor. The sedating properties are caused by H 1 blockade. The level of brain penetration (passage of the blood–brain barrier) is not fully determined by the lipophilicity (log P) of an individual compound. Compounds with a low or a high lipophilicity (log P) do not penetrate. For compounds with a basic centre the log D should be applied, replacing the log P; the log D corrects for the level of ionization of such compounds, as neutral species only readily enter into the CNS. For compounds with an intermediate log P or log D a Δlog P is introduced; a Δlog P indicates a large hydrogen binding capacity. A strong hydrogen binding capacity means a strong (serum) protein binding and consequently a poor brain penetration. Also the role of the P‐glycoprotein as a transporter out of the CNS is introduced. Finally the influence of histamine on the permeability of the blood–brain barrier is discussed; it is shown that histamine increases the extravasation of, for example, albumin.