Title:QSAR Modeling of Histamine H3R Antagonists/inverse Agonists as Future Drugs for Neurodegenerative Diseases
VOLUME: 16 ISSUE: 6
Author(s):Michelle Fidelis Correa* and Joao Paulo dos Santos Fernandes*
Affiliation:Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo, Rua Sao Nicolau 210, Centro 09913- 030, Diadema-SP, Departamento de Ciencias Farmaceuticas, Universidade Federal de Sao Paulo, Rua Sao Nicolau 210, Centro 09913- 030, Diadema-SP
Keywords:QSAR, H3 receptor, H3R antagonists, H3R inverse agonists, neurodegenerative diseases, neuropsychiatric disorders,
structure-activity relationship.
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.
