Validation of Sigma I Receptor Occupancy with Antipsychotic Ligands: A Molecular Perspective

Sigma-۱ receptors are unique and distinct class of receptors widely expressed in the central nervous system with involvement in regulation of various neutransmitters and are often over expressed in tumor cell lines of various tissues, such as melanoma, breast cancer, small lung carcinoma and prostate cancer. Accordingly, sigma ligands display anticancer activity in- vivo and in-vitro. In the present study, an attempt has been made to validate sigma-۱receptor and study its antipsychotic ligand interactions in a molecular perspective. C۶ cells (rat glioma)  grown in monolayers were exposed to haloperidol (sigma-۱ antagonist) and other anti-psychotic ligands and their relative cytotoxicity was determined by MTT assay to be ۴۲.۷۹ %, ۱۸.۹۶ %, ۲۴.۹۵ and ۲۲.۷۲% for haloperidol, ligand ۱, ligand ۲ and ligand ۳ respectively. Occupancy of sigma receptors with ligands through DNA laddering studies reveal the antipsychotic ligands modulate psychosis via sigma-۱receptor.

Keywords:

Haloperidol , antipsychotic ligands , Psychosis , Ssigma-۱ receptor , Anticancer