σ2 Receptors

Supporting information

σ2 receptors are members of the σ family of receptors that also includes σ1 receptors. Originally thought to be opioid receptors or the phencyclidine binding site on the NMDA receptor, they are now know to be distinct targets. These receptors are distinguished from σ1 receptors as they exhibit high affinity and stereoselectivity for the (-)-isomers of pentazocine, SK&F 10047 and cyclazocine, as well as having different tissue distribution patterns and subcellular localizations.

σ2 receptors are intracellular receptors located on the membranes of the mitochondria and endoplasmic reticulum. They are distributed throughout the central nervous system (especially the motor cortex area, cerebellum and substantia nigra pars) and in various peripheral tissues, including the liver, kidneys, lungs and muscles. They regulate Ca2+ release from endoplasmic reticulum stores, and so have a role in control of intracellular calcium signaling. Furthemore, σ2 receptors have also been shown to modulate the NMDA receptor complex, voltage-gated potassium channels and high-voltage-activated calcium channels.

There has been extensive study of σ receptors since their discovery over twenty years ago. σ ligands are thought to have the potential as pharmacological agents in modulation of mood disorders, amnesic and cognitive deficits, the effects produced by drug abuse, tardive dyskinesia and the potentiation of analgesia.

The σ2 receptor is currently uncharacterized.

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