Selective Sigma-1 (sigma_1) Receptor Antagonists: Emerging Target for the Treatment of Neuropathic Pain

摘要

A large number of therapeutic roles have been proposed for o receptors but the involvement of o receptor in non-acute pain had not been well explored up to now. o receptor knock-out mice became available offering us the possibility to study the role of G receptor in nociception, particularly in models where central sensitization processes play a significant role. Given the attractive therapeutic potential, we have developed a chemical program aimed at the discovery of novel and selective o ligands. Herein we discuss the rational basis of this approach and report preliminary pharmacological results of several chemical series and aspects of their structure-activity relationship on o receptor. Functional data in pain models are presented mainly on one series that provide evidence to consider selective o receptor antagonists an innovative and alternative approach for treating neuropathic pain.