Evidence from opiate binding studies that heroin acts through its metabolites

Life Sci. 1983:33 Suppl 1:773-6. doi: 10.1016/0024-3205(83)90616-1.


The relative affinity to opiate receptors of heroin, 6-acetylmorphine and morphine was estimated by determining their ability to displace specifically bound 3H-naltrexone from rat brain opiate binding sites. In vitro hydrolysis of heroin to 6-acetylmorphine was monitored in the binding assay filtrate by use of a quantitative HPLC procedure. The rate of heroin hydrolysis was significantly slower at 0 degrees C than at 37 degrees C. The displacement of 1 nM 3H-naltrexone by unlabeled ligand at concentrations ranging from 7 to 500 nM was measured at 0 degrees C for 120 minutes, yielding IC50 values of heroin = 483 nM, 6-acetylmorphine = 73 nM and morphine = 53 nM. When the binding data for heroin were recalculated to include the displacement that could be attributed to the 6-acetylmorphine derived from heroin degradation during the incubation, all of the apparent heroin binding was accounted for by the 6-acetylmorphine. These results are consistent with previous reports of the low binding affinity of morphine congeners (e.g., codeine) that lack a free phenolic 3-hydroxyl group and support the view that heroin is a prodrug which serves to determine the distribution of its intrinsically active metabolites, 6-acetylmorphine and morphine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Heroin / metabolism*
  • Heroin / pharmacology
  • Male
  • Morphine / pharmacology
  • Morphine Derivatives / pharmacology
  • Naltrexone / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*
  • Structure-Activity Relationship


  • Morphine Derivatives
  • Receptors, Opioid
  • Naltrexone
  • Heroin
  • Morphine
  • 6-O-monoacetylmorphine