Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain

Smith, Maree T. and Muralidharan, Arjun (2014) Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain. Expert Opinion On Therapeutic Targets, 19 1: 25-35. doi:10.1517/14728222.2014.957673


Author Smith, Maree T.
Muralidharan, Arjun
Title Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain
Journal name Expert Opinion On Therapeutic Targets   Check publisher's open access policy
ISSN 1472-8222
1744-7631
Publication date 2014-10-15
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1517/14728222.2014.957673
Open Access Status
Volume 19
Issue 1
Start page 25
End page 35
Total pages 11
Place of publication London, United Kingdom
Publisher Informa Healthcare
Collection year 2015
Language eng
Formatted abstract
Introduction: Neuropathic pain and chronic inflammatory pain are large unmet medical needs. Over the past two decades, numerous ’pain targets’ have been identified for analgesic drug discovery. Despite promising results in rodent pain models, many compounds modulating such targets lacked efficacy in clinical trials. An exception is oral EMA401, a small-molecule angiotensin II type 2 receptor (AT2R) antagonist.

Areas covered: Herein, angiotensin II/AT2R signaling-induced hyperexcitability and abnormal sprouting of cultured dorsal root ganglion neurons, together with radioligand binding, pharmacokinetics, analgesic efficacy and mode of action of small-molecule AT2R antagonists in rodent models of peripheral neuropathic and chronic inflammatory pain, are reviewed. The findings of a successful Phase IIa clinical trial of EMA401 in patients with neuropathic pain are presented in brief.

Expert opinion: The functional importance of angiotensin II/AT2R signaling has remained enigmatic for decades, and there are no clinically available medications that target the AT2R. However, on the basis of preclinical findings and recent clinical trial data showing that the peripherally restricted, small-molecule AT2R antagonist, EMA401, successfully alleviated neuropathic pain in a Phase II clinical trial, the AT2R is receiving considerable attention as a new therapeutic target with human validation for the relief of peripheral neuropathic and chronic inflammatory pain conditions.




Keyword Analgesia
Angiotensin II type 2 receptor
Chronic constriction injury-rat
Dideoxycytidine-rat
Freund’s compete adjuvant-rat
Inflammatory pain
Neuropathic pain
PCIBP-rat
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Posted online on October 15, 2014

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
School of Pharmacy Publications
Centre for Integrated Preclinical Drug Development Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Fri, 17 Oct 2014, 13:01:12 EST by Professor Maree Smith on behalf of School of Pharmacy