Structure‐Based Identification of Aporphines with Selective 5‐HT2AReceptor‐Binding Activity

• DOI: 10.1111/cbdd.12069
• Publication Date: 2012-10-05T17:59:28Z
• Authors: Vani Munusamy; Beow Keat Yap; Michael J. C. Buckle; Stephen W. Doughty; Lip Yong Chung
• Keywords: Radioligand; Docking (animal); Radioligand Assay

Selective blockade of the serotonin 5‐HT 2A receptor is a useful therapeutic approach for number disorders, including schizophrenia, insomnia and ischaemic heart disease. A series aporphines were docked into homology model rat using AutoDock. Selected compounds with high in silico binding affinities screened vitro radioligand‐binding assays against (5‐HT 1A ) dopamine (D1 D2) receptors. ( R )‐Roemerine (±)‐nuciferine found to have affinity K i = 62 139 n m , respectively), )‐roemerine showing 20‐ 400‐fold selectivity over D1 D2 Investigation ligand–receptor interactions suggested that due it having stronger H‐bonding dipole–dipole several key residues receptor‐binding site.