Abstract

Background: Histamine H3 receptor (H3R) is associated with several neuropsychological diseases, and thus it is an important target involved in several CNS disorders, such as narcolepsy, attention deficit hyperactivity disorder and schizophrenia. Since QSAR modeling is a feasible approach to explain the role of the molecular substituents in the biological activity, it can help in improving the design of better H3R ligands for these conditions.

Methods: This article reviews papers previously published in literature to show the current status of the contribution from QSAR modeling to reach H3R antagonists/inverse agonists.

Results: Classical and 3D-QSAR models were retrieved, showing that the steric and hydrophobic properties of the H3R ligands are most important to reach good affinity.

Conclusion: Although QSAR methods are valuable to design better H3R antagonists/inverse agonists, pharmacokinetics should also be considered in future models to ensure good CNS penetration.

Keywords: QSAR, H3 receptor, H3R antagonists, H3R inverse agonists, neurodegenerative diseases, neuropsychiatric disorders, structure-activity relationship.

Graphical Abstract