Evidence from opiate binding studies that heroin acts through its metabolites

C. E. Inturrisi, M. Schultz, S. Shin, J. G. Umans, L. Angel, E. J. Simon

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


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°C than at 37°C. The displacement of 1 nM 3H-naltrexone by unlabeled ligand at concentrations ranging from 7 to 500 nM was measured at 0°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.

Original languageEnglish (US)
Pages (from-to)773-776
Number of pages4
JournalLife Sciences
Issue numberSUPPL. 1
StatePublished - 1983
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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