Document Type : Original Article


1 School of Life Sciences, S. R. T. M. University, Nanded - 431606, India

2 School of Chemical Sciences, S. R. T. M. University, Nanded-431606, India


Sigma-1 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-1receptor and study its antipsychotic ligand interactions in a molecular perspective. C6 cells (rat glioma)  grown in monolayers were exposed to haloperidol (sigma-1 antagonist) and other anti-psychotic ligands and their relative cytotoxicity was determined by MTT assay to be 42.79 %, 18.96 %, 24.95 and 22.72% for haloperidol, ligand 1, ligand 2 and ligand 3 respectively. Occupancy of sigma receptors with ligands through DNA laddering studies reveal the antipsychotic ligands modulate psychosis via sigma-1receptor.

Graphical Abstract

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


Main Subjects

1. T.P. Su, T. Hayashi, T. Maurice, S. Buch, A.E. Ruoho, Trends Pharmacol. Sci. 2010, 31, 557.
2. R. Quirion, W.D. Bowen, Y. Itzhak, Trends Pharmacol Sci., 1992, 13, 85.
3. a) C.A. Buffington, S.A. Wolfe-Jr, J Urol. 1998, 160, 605; b) S.A. Wolfe-Jr, B.K. Ha, B.B. Whitlock, P. Saini, J Neuroimmunol. 1997, 72, 45.
4. T. Hayashi, T.P. Su, Cell. 2007, 131, 596.
5. D.B. Vaupel, Eur J Pharmacol. 1983, 92, 269.
6. B.J. Vilner, C.S. John, W.D. Bowen, Cancer Res 1995, 55, 408.
7. M.J. Muller, G. Grunder, H. Wetzel, F. Muller-Siecheneder, P. Marx-Dannigkeit. O. Benkert, Psychiatry
Res. 1999, 89, 275.
8. D. Fontanilla, M. Johannessen, A.R. Hajipour, N.V. Cozzi, M.B. Jackson, A.E. Ruoho, Science, 2009, 323, 934.
9. C.A. Maier, B. Wunsch, J. Med. Chem. 2002, 45, 438.
10. A.A. Rybczynska, R.A. Dierckx, K. Ishiwata, P.H. Elsinga, V.A. Waarde, J. Nucl. Med. 2008, 49, 2049.
11. T. Mossman, J. Immunol. Methods. 1983, 65, 55.
12. A.A. Rybczynska, R.A. Dierckx, K. Ishiwata, P.H. Elsinga, V.A. Waarde, J. Nucl. Med. 2008, 49, 2049.
13. B.J. Vilner,  C.S. John, W.D. Bowen, Cancer Res., 1995, 55, 408.