Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes

Abstract

The affinity of morphine, codeine, dihydrocodeine and their glucuronides for μ-, δ,- and κ-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [3H]DAMGO, [3H]DPDPE, and [3H]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the μ δ-ratio nor that of μ κ. Glucuronidation of the 6-hydroxyl group of morphine, codeine or dihydrocodeine did not affect the affinity to μ-receptors, slightly increased the affinity for δ-receptors and reduced the affinity for κ-receptors. The 6-glucuronides possess a decreased selectivity for μ- receptors over δ-receptors whereas that for μ- over κ-..