Pharmacological studies with a nonpeptidic, delta-opioid (-)-(1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH 11082)

European Journal of Pharmacology
Mario D AcetoCharles D Cook

Abstract

In the search for a selective delta-opioid receptor agonist, (-)-(1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH 11082) and the (+)-enantiomer were synthesized and tested. (-)-NIH 11082 displayed antinociceptive activity in the paraphenylquinone test (PPQ test) in male ICR mice [ED50=1.9 (0.7-5.3) mg/kg, s.c.] and showed little, if any, activity in the tail-flick and hot-plate assays. The (+)-enantiomer was essentially inactive indicating stereoselectivity. Opioid receptor subtype characterization studies indicated that naltrindole, a delta-opioid receptor antagonist, was potent versus the ED80 of (-)-NIH 11082 in the PPQ test [AD50=0.75 (0.26-2.20) mg/kg, s.c]. beta-Funaltrexamine and nor-binaltorphimine, selective mu- and kappa-receptor antagonists, respectively, were inactive versus the ED80 of (-)-NIH 11082. In rats with inflammation-induced pain, (-)-NIH 11082 produced antihyperalgesic effects that were attenuated by naltrindole. In morphine-dependent rhesus monkeys of both sexes, (-)-NIH 11082 neither substituted for morphine nor exacerbated withdrawal signs in the dose range of 4.0 to 32.0 mg/kg, s.c. Neither convulsions nor other overt behavioral signs were observed in any o...Continue Reading

References

Jan 5, 1993·European Journal of Pharmacology·P Y ChengH H Szeto
Jan 10, 1998·European Journal of Pharmacology·M D AcetoE R Bowman
Apr 26, 2000·British Journal of Pharmacology·G L FraserM N Perkins
May 24, 2000·European Journal of Pharmacology·T J HudzikA J Cross
Mar 14, 2001·European Journal of Pharmacology·J MikaB Przewłocka
Dec 21, 2004·The Journal of Pharmacology and Experimental Therapeutics·Charles D Cook, Michael D Nickerson

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Citations

Aug 13, 2011·Behavioural Pharmacology·Claire Gavériaux-Ruff, Brigitte Lina Kieffer
Sep 20, 2011·Trends in Pharmacological Sciences·Amynah A PradhanBrigitte L Kieffer
Oct 15, 2008·Peptides·Richard J Bodnar
Mar 3, 2015·Journal of Clinical Pharmacy and Therapeutics·J F Peppin, R B Raffa
Mar 20, 2014·British Journal of Pharmacology·Paul KlenowskiSelena E Bartlett
Mar 17, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rita TurnaturiLorella Pasquinucci
Aug 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Banulata GopalsamyEnoch Kumar Perimal
Jul 20, 2021·Chirality·José A GálvezMaría D Díaz-de-Villegas
Jul 6, 2010·Bioorganic & Medicinal Chemistry·Lorella PasquinucciGiuseppe Ronsisvalle

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