6-Monoacetylmorphine

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6-Monoacetylmorphine
6-monoacetylmorphine2DCSD.svg
Systematic (IUPAC) name
3-hydroxy-6-acetyl-(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan
Clinical data
Routes of
administration
Intravenous
Legal status
Legal status
Pharmacokinetic data
Biological half-life < 5 mins
Identifiers
CAS Number 2784-73-8 N
ATC code none
PubChem CID 5462507
ChemSpider 4575434 YesY
ChEMBL CHEMBL592009 YesY
Synonyms 6-acetylmorphine
Chemical data
Formula C19H21NO4
Molar mass 327.374 g/mol
 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 and then is 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 as an illicit drug 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]

Illicit production[edit]

The production of black tar heroin results in significant amounts of 6-MAM in the final product. This may be one of several reasons 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 appropriate catalyst to carry out the acetylation,{[1]}. g 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 and is common in cleaning agents and gardening supplies. 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. 6-MAM is approximately 30 percent more active than diacetylmorphine itself. This is why black tar heroin is generally more potent when the purity is similar. Black tar heroin is acetylated with acetic acid, thus only creating 6-MAM.

40 percent afghan heroin is equal to about 30 percent purity black tar[citation needed]. Most black tar heroin is between 55 and 93 percent purity[citation needed]. In black tar heroin the morphine is concentrated in liquid opium to approximately 90 percent purity[citation needed]. Instead of extracting the morphine from the opium, it is instead concentrated within the opium sap and acetylated as is. This is what gives it that gummy appearance. It is more or less concentrated and acetylated opium. Acetic acid is used and therefore only makes 6MAM. This is why black tar heroin by many is preferred, because the active drug has a 30 percent higher potency overall[citation needed].

Physical and chemical properties[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. doi:10.1016/0024-3205(83)90616-1. PMID 6319928. 
  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. doi:10.1016/0278-5846(84)90051-4. PMID 6543399. 
  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. doi:10.1073/pnas.85.14.5335. PMC 281745free to read. PMID 3393541.