Characterization of [(3)H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice.

TitleCharacterization of [(3)H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice.
Publication TypeJournal Article
Year of Publication2017
AuthorsYoo JHoon, Borsodi A, Tóth G, Benyhe S, Gaspar R, Matifas A, Kieffer BL, Metaxas A, Kitchen I, Bailey A
JournalNeurosci Lett
Volume643
Pagination16-21
Date Published2017 Mar 16
ISSN1872-7972
Abstract

Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear. This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [(3)H]oxymorphone revealed high affinity binding sites in mouse brain displaying Kd of 1.7nM and Bmax of 147fmol/mg. Furthermore, we performed quantitative autoradiography binding studies using [(3)H]oxymorphone in mouse brain. The distribution of [(3)H]oxymorphone binding sites was found to be similar to the selective MOP agonist [(3)H]DAMGO in the mouse brain. [(3)H]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [(3)H]oxymorphone binding sites suggesting oxymorphone may not target DOP or KOP. These results confirm that the MOP, and not the DOP or the KOP is the main high affinity binding target for oxymorphone.

DOI10.1016/j.neulet.2017.02.002
Alternate JournalNeurosci. Lett.
PubMed ID28192197

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