Document Detail


Evaluation of analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin-induced pain and hyperalgesia.
MedLine Citation:
PMID:  23324098     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The aim was to investigate the effects of AZD1940, a novel peripherally acting cannabinoid CB(1) / CB(2) receptor agonist, on capsaicin-induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects This was a randomized, double-blind, placebo-controlled, 4-sequences, 2-periods cross-over study in 44 male healthy volunteers aged 20-45 years. The effects of two single oral doses (400 μg and 800 μg) of AZD1940 were compared to placebo. Pain intensity after intradermal capsaicin injections in the forearm was assessed by continuous visual analogue scale (VAS, 0-100 mm). Primary and secondary hyperalgesia induced by application of capsaicin cream on the calf were assessed by measuring heat pain thresholds and area of mechanical allodynia, respectively. The CNS effects were assessed at baseline and up to 24 h after dosing using visual analogue mood scales (VAMS) for feeling 'stimulated', 'high', anxious', 'sedated' and 'down'. AZD1940 did not significantly attenuate either ongoing pain, primary or secondary hyperalgesia compared with placebo. Mild CNS effects were observed on the VAMS for 'high' and 'sedated' by AZD1940. Dose-dependent, mild to moderate, CNS-related and gastrointestinal adverse events were reported on treatment with AZD1940. No evidence of analgesic efficacy was found for a peripherally acting CB(1) / CB(2) receptor agonist in the human capsaicin pain model. The emergence of mild dose-dependent CNS effects suggests that the dose range predicted from preclinical data had been attained. © 2012 AstraZeneca R&D Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Authors:
Jarkko Kalliomäki; Peter Annas; Karin Huizar; Cyril Clarke; Annika Zettergren; Rolf Karlsten; Märta Segerdahl
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 AstraZeneca R&D Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Affiliation:
AstraZeneca R&D Södertälje, Sweden.
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