Selective small molecule angiotensin II type 2 (AT2) receptor antagonists for neuropathic pain: preclinical and clinical studies

Smith, Maree T., Anand, Praveen and Rice, Andrew S. C. (2016) Selective small molecule angiotensin II type 2 (AT2) receptor antagonists for neuropathic pain: preclinical and clinical studies. Pain, 157 Supplement 1: S33-S41. doi:10.1097/j.pain.0000000000000369


Author Smith, Maree T.
Anand, Praveen
Rice, Andrew S. C.
Title Selective small molecule angiotensin II type 2 (AT2) receptor antagonists for neuropathic pain: preclinical and clinical studies
Journal name Pain   Check publisher's open access policy
ISSN 0304-3959
1872-6623
Publication date 2016-02-01
Sub-type Article (original research)
DOI 10.1097/j.pain.0000000000000369
Open Access Status Not Open Access
Volume 157
Issue Supplement 1
Start page S33
End page S41
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2017
Language eng
Formatted abstract
Neuropathic pain affects up to 10% of the general population, but drug treatments recommended for the treatment of neuropathic pain are associated with modest efficacy and/or produce dose-limiting side effects. Hence, neuropathic pain is an unmet medical need. In the past 2 decades, research on the pathobiology of neuropathic pain has revealed many novel pain targets for use in analgesic drug discovery programs. However, these efforts have been largely unsuccessful as molecules that showed promising pain relief in rodent models of neuropathic pain generally failed to produce analgesia in early phase clinical trials in patients with neuropathic pain. One notable exception is the angiotensin II type 2 (AT2) receptor that has clinical validity on the basis of a successful double-blind, randomized, placebo-controlled, clinical trial of EMA401, a highly selective, orally active, peripherally restricted AT2 receptor antagonist in patients with postherpetic neuralgia. In this study, we review research to date on target validation, efficacy, and mode of action of small molecule AT2 receptor antagonists in rodent models of peripheral neuropathic pain and in cultured human sensory neurons, the preclinical pharmacokinetics of these compounds, and the outcome of the above clinical trial.
Keyword EMA401
Neuropathic pan
Analgesia
Inflammatory pain
Clinical trial
Angiotensin II type 2 receptor
Angiotensin II
Rodent neuropathic pain models
Postherpetic neuralgia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Review articles from the 5th International Meeting of the IASP Special Interest Group on Neuropathic Pain (NeuPSIG)

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Faculty of Medicine
School of Pharmacy Publications
 
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Created: Thu, 11 Feb 2016, 17:26:07 EST by Professor Maree Smith on behalf of School of Pharmacy