An update on the development of drugs for neuropsychiatric disorders: focusing on the sigma 1 receptor ligand.
The sigma1 receptor is an intracellular molecule that shares no homology with any mammalian proteins. sigma1 receptors normally localize at the endoplasmic reticulum and regulate a variety of signal transductions including intracellular Ca2+ dynamics and neurotrophic factor signaling. In the brain, sigma1 receptors are known to regulate the activity of diverse ion channels via protein-protein interactions. Accumulated evidences strongly indicate that the activation/upregulation of sigma1 receptors promotes the neuronal differentiation as well as a robust antiapoptotic action. In animals, sigma1 receptor agonists exhibit an antidepressant-like action. Furthermore, the agonists enhanced neuronal survival eventhough they were administered several hours after a brain ischemia. Thus, primary clinical targets of sigma1 receptor ligands are proposed to include stroke, neurodegenerative disorders and depression. Ligands for the sigma1 receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein.
Hayashi
Teruo
T
IRP, NIDA-NIH, Cellular Pathobiology Unit, Development and Plasticity Section, Cellular Neurobiology Research Branch, Room 3418, Triad building, 333 Cassell Drive, Baltimore, MD 21224, USA. thayashi@intra.nida.nih.gov
Su
Tsung-Ping
TP
D000818:Animals; D006801:Humans; D008024:Ligands; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D017480:Receptors, sigma / Q000737:chemistry / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000639:trends*; D000097605:Sigma-1 Receptor
D008024:Ligands; D004364:Pharmaceutical Preparations; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor