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Effects of a novel kappa opioid receptor agonist, TRK‐820, on intrathecal morphine‐induced itch and analgesia in monkeys
Author(s) -
Ko MeiChuan,
Husbands Stephen
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.712.4
Subject(s) - trk receptor , pharmacology , morphine , agonist , opioid receptor , opioid , medicine , κ opioid receptor , antipruritic , scratching , antagonist , mechanism of action , receptor , chemistry , biochemistry , physics , acoustics , in vitro , neurotrophin
Itch (Pruritus) is the most common side effect associated with spinal administration of morphine given to humans for analgesia. Recent studies have suggested that kappa opioid receptor (KOR) agonists can attenuate intrathecal morphine‐induced itch/scratching responses. TRK‐820 has been shown to be a potent high efficacy KOR agonist with a low efficacy mu opioid agonist action. The aim of the study was to investigate the effectiveness of TRK‐820 as an antipruritic and to elucidate the receptor mechanisms underlying TRK‐820's antipruritic effect. Adult rhesus monkeys were used in various behavioral assays for measuring itch/scratching, analgesia, and respiratory depression. Systemic administration of TRK‐820 (0.1–1 μg/kg, i.m.) dose‐dependently attenuated intrathecal morphine (30 μg)‐induced scratching responses without affecting morphine‐induced antinociception. Pretreatment with 1 μg/kg of TRK‐820 did not significantly change the dose‐response curves of systemic morphine‐induced antinociception and respiratory depression. In addition, a selective KOR antagonist, GNTI (1 mg/kg), significantly reversed the antipruritic effect of TRK‐820. Taken together, these results indicated that TRK‐820's antipruritic action was mediated by a KOR agonist action without a mu opioid antagonist action. This receptor mechanism‐based finding supports the clinical potential of KOR agonists as antipruritics to treat mu opioid receptor‐mediated pruritus (Supported by USPHS Grant DA‐013685).