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Inability of an opioid antagonist lacking negative intrinsic activity to induce opioid receptor up‐regulation in vivo
Author(s) -
Morris B.J.,
Millan M.J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12271.x
Subject(s) - (+) naloxone , opioid , μ opioid receptor , agonist , antagonist , opioid receptor , pharmacology , chemistry , in vivo , κ opioid receptor , intrinsic activity , receptor , morphine , nociception , naltrexone , medicine , endocrinology , biology , microbiology and biotechnology
1 It has recently been suggested that opioid antagonists may be divided into those possessing negative intrinsic activity (e.g. naloxone) and those with neutral intrinsic activity (e.g. MR2266). 2 MR2266 was chronically administered to rats by subcutaneous infusion at a dose of 0.3 mg kg −1 h −1 for 1 week. 3 This dose reduced ingestive behaviour and blocked the antinociceptive effects of a κ‐agonist, indicating occupation of opioid receptors in vivo . 4 No supersensitivity could be detected to the antinociceptive actions of μ or κ agonists, either one or two days after cessation of treatment. 5 No up‐regulation of μ, δ or κ binding sites was observed. 6 Since naloxone induces both supersensitivity and receptor up‐regulation under equivalent conditions, the results suggest that negative intrinsic activity may be required for these phenomena to occur.