title: Evidence from opiate binding studies that heroin acts through its metabolites.
abstract: 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.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003932:Heroin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009022:Morphine Derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D009022:Morphine Derivatives; D011957:Receptors, Opioid; D009271:Naltrexone; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine