Mu receptor binding of some commonly used opioids and their metabolites

Life Sci. 1991;48(22):2165-71. doi: 10.1016/0024-3205(91)90150-a.


The binding affinity to the mu receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding (e.g. morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM). Decreasing the length of the alkyl group at position 3 decreased the Ki values (morphine less than codeine less than ethylmorphine less than pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 (e.g. hydrocodone, Ki = 19.8 nM) had relatively weak receptor binding, whilst their O-demethylated metabolites (e.g. hydromorphone, Ki = 0.6 nM) had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Codeine / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / metabolism*
  • Male
  • Morphine / metabolism*
  • Morphine Derivatives / metabolism
  • Narcotics / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, mu
  • Structure-Activity Relationship


  • Enkephalins
  • Morphine Derivatives
  • Narcotics
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Morphine
  • Codeine