In Silico Repositioning of Dopamine Modulators with Possible Application to Schizophrenia: Pharmacophore Mapping, Molecular Docking and Molecular Dynamics Analysis.

ABSTRACT: We have performed theoretical calculations with 70 drugs that have been considered in 231 clinical trials as possible candidates to repurpose drugs for schizophrenia based on their interactions with the dopaminergic system. A hypothesis of shared pharmacophore features was formulated to support our calculations. To do so, we have used the crystal structure of the D2-like dopamine receptor in complex with risperidone, eticlopride, and nemonapride. Linagliptin, citalopram, flunarizine, sildenafil, minocycline, and duloxetine were the drugs that best fit with our model. Molecular docking calculations, molecular dynamics outcomes, blood-brain barrier penetration, and human intestinal absorption were studied and compared with the results. From the six drugs selected in the shared pharmacophore

SUBMITTER: Mejia-Gutierrez M 

PROVIDER: S-EPMC8209794 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature