Heroin human metabolism

Heroin (3,6-diacetylmorphine or diamorphine) was originally synthesized from morphine and is regarded as one of the most dangerous dmgs of abuse. The human metabolism of heroin is presented in Fig. 2.4 its main metabohtes are reported in Table 2.1. It is rapidly deacetylated to 6-acetylmorphine, which is further hydrolyzed to morphine in the liver. The first reaction is catalyzed by blood esterases, while the second occurs in the liver (Baselt, 2004). 

Maurer, H. H., C. Sauer, and D. S. Theobald. 2006. Toxicokinetics of drugs of abuse Current knowledge of isomers involved in the human metabolism of tetrahydrocarmabinol, cocaine, heroin, morphine, and codeine. Therapeut DrugMonit 28 447 53. 

Shi J, Hui L, Xu Y, et al Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat 19 459 60, 2002 Shinderman M, Maxwell S, Brawand-Arney M, etal Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Dependence 69 205-211, 2003... 

Heroin is rapidly metabolized in humans 22 and other species 451 452 to 6-acetylmorphine and morphine, the active metabolites/100 Compounds lacking a free 3-0 H function bind poorly to opioid receptor preparations, and heroin was no exception. Morphine and 6-acetylmorphine bound well to receptor preparations, and the binding of the latter accounted for all the apparent binding of heroin. In addition to 6-acetylmorphine and morphine, the 3-glucuronide of morphine (261) occurred as a major metabolite of heroin... 

Bencharit, S., Morton, G. L., Xue, Y, Potter, P. M., Redinbo, M. (2003). Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nature Structural... 

Early studies of the disposition and metabolism of heroin in humans and animals were performed with PC and TLC. Heroin, 6-acetylmorphine, and morphine were separated by normal-phase and reversed-phase chromatographic systems. The analytes were visualized by spraying with iodopla-tinate, Folin-Ciocalteu reagent, or Dragendorff s reagent. 

The dose used at the beginning is approximately 10 mg, but addicted subjects can use up to 1 or 2 g, with an estimated average dose of 30 mg (Table 2.2). Heroin has very httle afhnity for the opiate receptors in brain and exerts its effects only after metabolism to 6-acety hnorphine and morphine catalyzed in the liver by human caiboxylesterase (hCE-1 and hCE-2), in semm by pseudocholinesterase, and also nonenzymatically (Maurer et al., 2006). 

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