6-Monoacetylmorphine

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6-Monoacetylmorphine
Structural formula
Ball-and-stick model
Clinical data
Synonyms 6-acetylmorphine
Routes of
administration
Intravenous
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Biological half-life < 5 mins
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEMBL
ECHA InfoCard 100.150.555
Chemical and physical data
Formula C19H21NO4
Molar mass 327.374 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

6-Monoacetylmorphine (6-MAM) or 6-acetylmorphine (6-AM) is one of three active metabolites of heroin (diacetylmorphine), the others being morphine and the much less active 3-monoacetylmorphine (3-MAM).

Pharmacology[edit]

6-MAM occurs as a metabolite of heroin. Once it has passed first-pass metabolism, 6-MAM is then metabolized into morphine or excreted in urine.

Heroin is rapidly metabolized by esterase enzymes in the brain and has an extremely short half-life. It has also relatively weak affinity to μ-opioid receptors because the 3-hydroxy group, essential for effective binding to the receptor, is masked by the acetyl group. Therefore, heroin acts as a pro-drug, serving as a lipophilic transporter for the systemic delivery of morphine, which actively binds with μ-opioid receptors.[1][2]

6-MAM already has a free 3-hydroxy group and shares the high lipophilicity of heroin, so it penetrates the brain just as quickly and does not need to be deacetylated at the 6-position in order to be bioactivated; this makes 6-MAM somewhat more potent than heroin.[3]

Availability[edit]

6-MAM is rarely encountered in an isolated form due to the difficulty in selectively acetylating morphine at the 6-position without also acetylating the 3-position. However, it is found in significant amounts in black tar heroin with diacetylmorphine.

Synthesis[edit]

The production of black tar heroin results in significant amounts of 6-MAM in the final product. 6-MAM is approximately 30 percent more active than diacetylmorphine itself,[citation needed] This is why despite lower heroin content, black tar heroin may be more potent than some other forms of heroin. 6-MAM can be synthesized from morphine using glacial acetic acid with an organic base as a catalyst. The acetic acid must be of a high purity (97-99 per cent) for the acid to properly acetylate the morphine at the 6th position effectively creating 6-MAM. Acetic acid is used rather than acetic anhydride, as acetic acid is not strong enough to acetylate the phenolic 3-hydroxy group but is able to acetylate the 6-hydroxy group, thus selectively producing 6-MAM rather than heroin. Acetic acid is a convenient way to produce 6-MAM, as acetic acid also is not a watched chemical as it is the main component of vinegar.

Chemistry[edit]

Detection in bodily fluids[edit]

Since 6-MAM is a unique metabolite to heroin, its presence in the urine confirms that heroin was the opioid used. This is significant because on a urine immunoassay drug screen, the test typically tests for morphine, which is a metabolite of a number of legal and illegal opiates/opioids such as codeine, morphine sulfate, and heroin. Trace amounts of 6-MAM, a specific metabolite of heroin, are also excreted for approximately 6–8 hours following heroin use.[4] so a urine specimen must be collected soon after the last heroin use, however, the presence of 6-MAM suggests that heroin was used as recently as within the last day. 6-MAM is naturally found in the brain of certain mammals.[5]

See also[edit]

  • M3G, morphine-3-glucuronide an inactive metabolite of morphine much as 3-MAM is the less active metabolite of heroin (notably here as morphine is an active secondary metabolite of heroin itself with 6-Monoacetylmorphine being the intermediate stage)
  • M6G, morphine-6-glucuronide the active variant in close relation to 6-MAM, being relative as twin metabolites of this articles very metabolite itself, morphine, twinned to a metabolite (3-MAM) of a parent compound (heroin) of this article's chemical
Acetyl groups of heroin. In 6-MAM upper group is changed to hydrogen making hydroxyl-group in 3-position.

References[edit]

  1. ^ "Evidence from opiate binding studies that heroin acts through its metabolites". Life Sci. 33 Suppl 1: 773–6. 1983. PMID 6319928. doi:10.1016/0024-3205(83)90616-1. 
  2. ^ Ricerca Italiana - PRIN - Role of morphine glucuronides in heroin addiction
  3. ^ "Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine". Prog. Neuropsychopharmacol. Biol. Psychiatry. 8 (4-6): 747–50. 1984. PMID 6543399. doi:10.1016/0278-5846(84)90051-4. 
  4. ^ https://www.redwoodtoxicology.com/resources/drug_info/opiates
  5. ^ "6-Acetylmorphine: a natural product present in mammalian brain". Proc. Natl. Acad. Sci. U.S.A. 85 (14): 5335–8. July 1988. PMC 281745Freely accessible. PMID 3393541. doi:10.1073/pnas.85.14.5335.