Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain.
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.
Díaz
José Luis
JL
Department of Chemistry, ESTEVE, Av. Mare de Déu de Montserrat 221, 08041 Barcelona, Spain. jldiaz@esteve.es
Zamanillo
Daniel
D
Corbera
Jordi
J
Baeyens
José Manuel
JM
Maldonado
Rafael
R
Pericàs
Miquel Angel
MA
Vela
José Miguel
JM
Torrens
Antoni
A
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
D000701:Analgesics, Opioid; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor