title: Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain.
abstract: A large number of therapeutic roles have been proposed for sigma(1) receptors but the involvement of sigma(1) receptor in non-acute pain had not been well explored up to now. sigma(1) receptor knock-out mice became available offering us the possibility to study the role of sigma(1) 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 sigma(1) 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 sigma(1) receptor. Functional data in pain models are presented mainly on one series that provide evidence to consider selective sigma(1) receptor antagonists an innovative and alternative approach for treating neuropathic pain.
authors.affiliation: Department of Chemistry, ESTEVE, Av. Mare de Déu de Montserrat 221, 08041 Barcelona, Spain. jldiaz@esteve.es
authors.forename: José Luis
authors.initials: JL
authors.lastname: Díaz
authors.forename: Daniel
authors.initials: D
authors.lastname: Zamanillo
authors.forename: Jordi
authors.initials: J
authors.lastname: Corbera
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Baeyens
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Miquel Angel
authors.initials: MA
authors.lastname: Pericàs
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Vela
authors.forename: Antoni
authors.initials: A
authors.lastname: Torrens
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000097605:Sigma-1 Receptor
chemical_list: D000701:Analgesics, Opioid; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor