title: Mu receptor binding of some commonly used opioids and their metabolites.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Chen
authors.forename: R J
authors.initials: RJ
authors.lastname: Irvine
authors.forename: A A
authors.initials: AA
authors.lastname: Somogyi
authors.forename: F
authors.initials: F
authors.lastname: Bochner
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003061:Codeine / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism; D009294:Narcotics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D013329:Structure-Activity Relationship
chemical_list: D004745:Enkephalins; D009022:Morphine Derivatives; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D003061:Codeine