Brain research bulletin
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Brain research bulletin · Jul 2001
SoRI 9409, a non-peptide opioid mu receptor agonist/delta receptor antagonist, fails to stimulate [35S]-GTP-gamma-S binding at cloned opioid receptors.
Recent work suggests that opioids which combine mu agonist and delta antagonist activity may be non-addicting antinociceptive agents. SoRI 9409 (5'-(4-Chlorophenyl)-17-(cyclopropylmethyl)-6,7-didehydro-3,14-dihydroxy-4,5alpha-epoxypyrido-[2',3':6,7]morphinan) is a naltrexone-derived non-peptide ligand which demonstrates partial mu and kappa agonist activity and antagonist activity at delta receptors. Chronic administration of SoRI 9409 to mice failed to produce tolerance to its antinociceptive effect and SoRI 9409 produced less withdrawal signs than naloxone in acute and chronic morphine dependence models. ⋯ Its profile of activity resembled that of naltrindole (NTI). Viewed collectively, the in vitro data reported here predict that SoRI 9409 should be a mu antagonist in vivo, which is not observed. Resolving these discrepant findings will require additional research.