Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes.
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 [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 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 over delta-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.
Mignat
C
C
Institute of Pharmacology, University of Kiel, Germany.
Wille
U
U
Ziegler
A
A
D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003061:Codeine / Q000031:analogs & derivatives* / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism*; D006168:Guinea Pigs; D009020:Morphine / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014316:Tritium
D044482:Benzeneacetamides; D004745:Enkephalins; D005965:Glucuronates; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593; C014481:dihydrocodeine; D003061:Codeine