Early development of sigma-receptor ligands
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Updated: Jun 3, 2026

Detection of Ligand-activated G Protein-coupled Receptor Internalization by Confocal Microscopy
Published on: April 9, 2017
Sanju Narayanan1, Rohit Bhat, Christophe Mesangeau
1Departments of Medicinal Chemsitry, School of Pharmacy, The University of Mississippi, MS 38655, USA.
Abstract:
Sigma receptors (σ-1 and σ-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The σ-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K(+)- and Ca(2+)-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. σ-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. σ-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. σ 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 σ receptor-specific ligands and radiolabeling agents.
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