Activation of G-Proteins by Morphine and Codeine Congeners: Insights to the Relevance of O- and N-Demethylated Metabolites at μ- and δ-Opioid Receptors

  title={Activation of G-Proteins by Morphine and Codeine Congeners: Insights to the Relevance of O- and N-Demethylated Metabolites at $\mu$- and $\delta$-Opioid Receptors},
  author={Chad M Thompson and Heidi L. Wojno and Elisabeth Greiner and Everette L. May and Kenner C. Rice and Dana E Selley},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={547 - 554}
Phenotypic differences in analgesic sensitivity to codeine (3-methoxymorphine) results from polymorphisms in cytochrome P450–2D6, which catalyzes O-demethylation of codeine to morphine. However, O-demethylation reportedly is not required for analgesic activity of the 7,8-saturated codeine congeners dihydrocodeine, hydrocodone, and oxycodone. This study determined the potency and efficacy of these compounds and their demethylated derivatives to stimulate μ- and δ-opioid receptor-mediated G… 

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