AFFINITY PROFILES OF MORPHINE, CODEINE, DIHYDROCODEINE AND THEIR GLUCURONIDES AT OPIOID RECEPTOR SUBTYPES

摘要

The affinity of morphine, codeine, dihydrocodeine and their glucuronides for mu-, delta-, and kappa-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [H-3]DAMGO, [H-3]DPDPE, and [H-3]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the mu/delta ratio nor that of mu/kappa. Glucuronidation of the 6-hydroxyl group of morphine, codeine or dihydrocodeine did not affect the affinity to mu-receptors, slightly increased the affinity for delta-receptors and reduced the affinity for kappa-receptors. The 6-glucuronides possess a decreased selectivity for mu-receptors whereas that for mu- over kappa-receptors was increased. It is concluded that chemical variations at 3- and 6-position of morphine independently affect the affinity to opioid receptor subtypes. [References: 20]