Early development of sigma-receptor ligands

Sigma receptors (sigma-1 and sigma-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The sigma-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K+- and Ca2+-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. sigma-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. sigma-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. sigma receptors bind to a diverse class of pharmacological compounds like cocaine, methamphetamine, benzomorphans like (+/-)-pentazocine, (+/-)-SKF-10,047 and endogenous neurosteroids and sphingolipids. In this review we focus on the early development of a receptor-specific ligands and radiolabeling agents.