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

被引：42

作者：

Borsook, David ^{[1
,2
]}

Upadhyay, Jaymin ^{[1
]}

Klimas, Michael ^{[3
]}

Schwarz, Adam J. ^{[4
]}

Coimbra, Alexandre ^{[3
]}

Baumgartner, Richard ^{[3
]}

George, Edward ^{[1
]}

Potter, William Z. ^{[3
]}

Large, Thomas ^{[5
]}

Bleakman, David ^{[4
]}

Evelhoch, Jeffrey ^{[3
]}

Iyengar, Smriti ^{[4
]}

Becerra, Lino ^{[1
,2
]}

Hargreaves, Richard J. ^{[3
]}

机构：

[1] McLean Hosp, PAIN Grp, Brain Imaging Ctr, Belmont, MA 02478 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA

[3] Merck Res Labs, West Point, PA 19486 USA

[4] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[5] Sunov Pharmaceut Inc, Marlborough, MA 01752 USA

来源：

DRUG DISCOVERY TODAY | 2012年 / 17卷 / 17-18期

关键词：

POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSIVE DISORDER; CENTRAL-NERVOUS-SYSTEM; P NK1 RECEPTOR; SUBSTANCE-P; NEUROPATHIC PAIN; NEUROKININ-1; ANTAGONIST; TACHYKININ NK1; HUMAN BRAIN; GUINEA-PIG;

D O I：

10.1016/j.drudis.2012.05.004

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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.

引用

页码：964 / 973

页数：10

共 85 条

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