sigma Receptors have been implicated in many pharmacological and physiological functions. sigma Receptors were purported to modulate behavioral alteration induced by cocaine and amphetamine, mediate effects of certain atypical antipsychotic agents, affect tonic potassium channels, the PCP/NMDA receptor complex, duodenal bicarbonate secretion, and CRF-induced colonic motility. sigma Receptors were reported to be altered in schizophrenia in certain studies, and up- and downregulations of sigma receptors have been observed in certain conditions. Neuropeptide Y has been shown to modulate the PCP/NMDA receptor complex in both central and gastrointestinal systems via sigma receptors. sigma Receptors are G-protein linked, and certain actions of sigma receptor ligands were affected by G-protein-modifying agents. Using photoaffinity labeling technique, a polypeptide of about 26 kDa has been identified as a sigma receptor. However, the exact biochemical relationship of this polypeptide to sigma receptors is unknown at present.