Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy

Smith, Maree T., Lau, Tanya, Wallace, Victoria C. J., Wyse, Bruce D. and Rice, Andrew S. C. (2014) Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy. Behavioural Pharmacology, 25 2: 137-146. doi:10.1097/FBP.0000000000000025


Author Smith, Maree T.
Lau, Tanya
Wallace, Victoria C. J.
Wyse, Bruce D.
Rice, Andrew S. C.
Title Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy
Journal name Behavioural Pharmacology   Check publisher's open access policy
ISSN 0955-8810
1473-5849
Publication date 2014-04
Sub-type Article (original research)
DOI 10.1097/FBP.0000000000000025
Open Access Status
Volume 25
Issue 2
Start page 137
End page 146
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2015
Language eng
Formatted abstract
Individuals infected with the HIV and taking certain antiretroviral drugs to suppress viral replication have a high prevalence of neuropathic pain that is not alleviated by analgesic/adjuvant drugs that are often efficacious for the relief of other types of neuropathic pain. There is therefore a great need for new analgesics to alleviate the pain of antiretroviral toxic neuropathy (ATN). Small-molecule angiotensin II type 2 receptor (AT2R) antagonists, with >=1000-fold selectivity over the angiotensin II type 1 receptor, produced analgesia in the chronic constriction injury of the sciatic nerve rat model of peripheral nerve trauma. Hence, the present study was designed to assess their analgesic efficacy in a rat model of ATN. The analgesic efficacy of small-molecule AT2R antagonists (EMA200 and EMA300) was assessed in a rat model of dideoxycytidine (ddC)-induced ATN. Single intraperitoneal bolus doses of EMA200 (0.3–10 mg/kg) induced dose-dependent analgesia in ddC-rats; the mean ED50 was 3.2 mg/kg. Twice-daily intraperitoneal administration of EMA300 at 30 mg/kg to ddC-rats for 3 days produced significant analgesia on days 2 and 3 of the treatment period. Therefore, small-molecule AT2R antagonists should be investigated further as novel analgesics for the relief of ATN.
Keyword Analgesia
Angiotensin II type 2 receptor antagonists
Antiretroviral drug induced neuropathy
Antiretroviral toxic neuropathy
EMA200
EMA300
HIV-associated sensory neuropathy
HIV-SN
Mechanical hypersensitivity
Neuropathic pain
Angiotensin II type 2 receptor (AT2R) antagonists
ATN
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 22 Mar 2014, 17:19:28 EST by Professor Maree Smith on behalf of Centre for Integrated Preclinical Drug Development