Central Nervous System Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Central Nervous System Agents)


Selective Sigma-1 (σ1) Receptor Antagonists: Emerging Target for the Treatment of Neuropathic Pain

Author(s): Jose Luis Diaz, Daniel Zamanillo, Jordi Corbera, Jose Manuel Baeyens, Rafael Maldonado, Miquel Angel Pericàs, Jose Miguel Vela and Antoni Torrens

Affiliation: Department of Chemistry,ESTEVE, Av. Mare de Deu de Montserrat 221, 08041 Barcelona, Spain.


A large number of therapeutic roles have been proposed for σ1 receptors but the involvement of σ1 receptor in non-acute pain had not been well explored up to now. σ1 receptor knock-out mice became available offering us the possibility to study the role of σ1 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 σ1 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 σ1 receptor. Functional data in pain models are presented mainly on one series that provide evidence to consider selective σ1 receptor antagonists an innovative and alternative approach for treating neuropathic pain.

Keywords: Neuropathic pain, analgesia, sigma-1 antagonists, sigma-1 knock-out, central sensitization

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Article Details

Page: [172 - 183]
Pages: 12
DOI: 10.2174/1871524910909030172