QSAR Modeling of Histamine H(3)R Antagonists/inverse Agonists as Future Drugs for Neurodegenerative Diseases

BACKGROUND: Histamine H(3) receptor (H(3)R) 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 H(3)R 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 H(3)R antagonists/inverse agonists. RESULTS: Classical and 3D-QSAR models were retrieved, showing that the steric and hydrophobic properties of the H(3)R ligands are most important to reach good affinity. CONCLUSION: Although QSAR methods are valuable to design better H(3)R antagonists/inverse agonists, pharmacokinetics should also be considered in future models to ensure good CNS penetration.