title: The apparent affinity of morphine-3-glucuronide at mu1-opioid receptors results from morphine contamination: demonstration using HPLC and radioligand binding.
abstract: Equilibrium binding studies in sheep thalamic homogenates indicated that morphine-3-glucuronide (M3G) had an apparent affinity for mu1-opioid binding sites (IC50 = 178 +/- 40 nM, Ki = 116 +/- 25 nM, mean +/- s.e.m., n = 4) similar to that reported by Pasternak and co-workers (1). However, when the chemical purity of M3G was investigated using high-performance-liquid-chromatography (HPLC) with electrochemical detection, it was found to be contaminated with 0.5% (molar basis) of morphine. Reduction of the morphine contamination of M3G to 0.08% resulted in a 7.2-fold decrease in apparent binding affinity (IC50 = 1279 +/- 287 nM, Ki = 766 +/- 30 nM, mean +/- s.e.m., n = 4), indicating that the small percentage of morphine present in the M3G raw material drug is the likely explanation for M3G's apparent binding to mu1-opioid receptors.
authors.affiliation: Department of Pharmacy, University of Queensland, Brisbane, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Bartlett
authors.forename: M T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D009020:Morphine / Q000032:analysis*; D009022:Morphine Derivatives / Q000302:isolation & purification* / Q000378:metabolism*; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012756:Sheep; D013788:Thalamus / Q000378:metabolism
chemical_list: D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; D009020:Morphine; C018108:morphine-3-glucuronide