Subtype selectivity of dopamine receptor ligands: insights from structure and ligand-based methods.

ABSTRACT: Subtype selective dopamine receptor ligands have long been sought after as therapeutic and/or imaging agents for the treatment and monitoring of neurologic disorders. We report herein on a combined structure- and ligand-based approach to explore the molecular mechanism of the subtype selectivity for a large class of D₂-like dopamine receptor ligands (163 ligands in total). Homology models were built for both human D(₂L) and D₃ receptors in complex with haloperidol. Other ligands, which included multiple examples of substituted phenylpiperazines, were aligned against the binding conformations of haloperidol, and three-dimensional quantitative structure activity relationship (3D-QSAR) analyses were carried out. The receptor models show that although D₂ and D₃ share highly similar folds and 3

SUBMITTER: Wang Q 

PROVIDER: S-EPMC4022043 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature