Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects.
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Weerts EM, Kim YK, Wand GS, Dannals RF, Lee JS, Frost JJ, McCaul ME
Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects.
Neuropsychopharmacology. 2008 Feb;33(3):653-65. Epub 2007 May 9.
- PubMed ID
- 17487229 [ View in PubMed]
- Abstract
Blockade of brain mu-opioid receptor (mu-OR) and delta-opioid receptor (delta-OR) was investigated in recently abstinent alcohol-dependent subjects (N=21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-beta-naltrexol. Regional brain mu-OR binding potential (BP) and delta-OR Ki was measured using [11C]carfentanil (CAR) positron emission tomography (PET) and [11C]methyl naltrindole ([11C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [11C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean+SD% inhibition=94.9+4.9%). Naltrexone only partially inhibited the [11C]MeNTI Ki and there was more variability across subjects (mean+SD% inhibition=21.1+14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of delta-OR Ki in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of mu-OR BP. Peak levels of 6-beta-naltrexol were not significantly correlated with % inhibition of mu-OR BP or delta-OR Ki. Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the mu-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of delta-OR and greater variability in delta-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in delta-OR blockade by naltrexone and clinical outcomes should be explored.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Naltrexone Delta-type opioid receptor Protein Humans YesAntagonistDetails Naltrexone Mu-type opioid receptor Protein Humans YesAntagonistDetails