Decision-making using fMRI in clinical drug development: revisiting NK-1 receptor antagonists for pain

Drug Discovery Today
David BorsookRichard J Hargreaves

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.

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Jan 15, 2013·Current Pain and Headache Reports·Collin F M Clarke, Keith St Lawrence
Jul 19, 2013·Translational Psychiatry·D BorsookM Fava
Oct 26, 2013·European Journal of Pharmacology·Paul L R Andrews, Gareth J Sanger
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Aug 15, 2014·Science Translational Medicine·David BorsookFrank Porreca
Mar 8, 2014·World Journal of Gastroenterology : WJG·Miguel Muñoz, Rafael Coveñas
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Sep 14, 2018·Current Medicinal Chemistry·Charlene Gadais, Steven Ballet
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Feb 27, 2020·International Journal of Molecular Sciences·David O Lyons, Nicholas A Pullen
Jan 6, 2021·Current Allergy and Asthma Reports·Monica ThapaliyaHydar Ali

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