title: Decision-making using fMRI in clinical drug development: revisiting NK-1 receptor antagonists for pain.
abstract: Substance P (SP) and neurokinin-1 receptors (NK-1R) are localized within central and peripheral sensory pain pathways. The roles of SP and NK-1R in pain processing, the anatomical distribution of NK-1R and efficacy observed in preclinical pain studies involving pain and sensory sensitization models, suggested that NK-1R antagonists (NK-1RAs) would relieve pain in patient populations. Despite positive data available in preclinical tests for a role of NK-1RAs in pain, clinical studies across several pain conditions have been negative. In this review, we discuss how functional imaging-derived information on activity in pain-processing brain regions could have predicted that NK-1RAs would have a low probability of success in this therapeutic domain.
authors.affiliation: Imaging Consortium for Drug Development, USA. David.Borsook@childrens.harvard.edu
authors.forename: David
authors.initials: D
authors.lastname: Borsook
authors.forename: Jaymin
authors.initials: J
authors.lastname: Upadhyay
authors.forename: Michael
authors.initials: M
authors.lastname: Klimas
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.forename: Alexandre
authors.initials: A
authors.lastname: Coimbra
authors.forename: Richard
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Edward
authors.initials: E
authors.lastname: George
authors.forename: William Z
authors.initials: WZ
authors.lastname: Potter
authors.forename: Thomas
authors.initials: T
authors.lastname: Large
authors.forename: David
authors.initials: D
authors.lastname: Bleakman
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Evelhoch
authors.forename: Smriti
authors.initials: S
authors.lastname: Iyengar
authors.forename: Lino
authors.initials: L
authors.lastname: Becerra
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
mesh_terms: D000818:Animals; D003657:Decision Making; D055808:Drug Discovery; D006801:Humans; D008279:Magnetic Resonance Imaging; D064729:Neurokinin-1 Receptor Antagonists; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018040:Receptors, Neurokinin-1 / Q000502:physiology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1