Identifying potential dopamine receptor D2 antagonist from Rauwolfia serpentina An in-silico virtual screening approach

Abstract

BackgroundTo combat the alarming rise of neuropsychiatric diseases like Schizophrenia, new drugs with fewer side effects have to be identified and characterized for the symptomatic treatment of Scz. Positive symptoms associated with Scz are hallucinations and delusions mainly due to the overactivation of the D2 dopaminergic receptors in the cortical pathways. D2 receptor antagonists identified from Rauwolfia serpentina are employed for controlling positive symptoms. Materials and methodsThe IMPPAT database was used to identify phytoconstituents from the root of Rauwolfia serpentina that can be used for antagonizing D2 dopaminergic receptor. 39 compounds were identified and SDF files were obtained from the PubChem database molecular docking with the modelled dopamine D2 receptor was used as a virtual screening tool followed by ADMET screening of the potential lead compound. ResultsAfter docking analysis, 11 compounds having binding affinity [≥] -9 kcal/mol were shortlisted for ADMET analysis. After analysis, 4 compounds (1,2-dihydrovomilenine, Corynanthine, Rauwolscine, and Yohimbine) were identified as potential leads. Among these 4 compounds, 1,2-dihydrovomelenine has been identified as the lead compound. ConclusionThe present study identified a potential new therapeutic compound that can be used for controlling the positive symptoms of Scz patients in vitro as well as in vivo.