6-monoacetylmorphine

同

MAM

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/07 07:13:37」(JST)

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6-Monoacetylmorphine

Systematic (IUPAC) name
3-hydroxy-6-acetyl-(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan
Clinical data
Legal status	AU: Prohibited (S9) UK: Class A US: Schedule I
Routes of administration	Intravenous
Pharmacokinetic data
Biological half-life	< 5 mins
Identifiers
CAS Registry Number	2784-73-8 N
ATC code	None
PubChem	CID: 5462507
ChemSpider	4575434 Y
ChEMBL	CHEMBL592009 Y
Synonyms	6-acetylmorphine
Chemical data
Formula	C19H21NO4
Molecular mass	327.374 g/mol
SMILES CC(=O)c3cc(O)c1O[C@@H]4[C@]25CCN(C)[C@H](Cc3c12)[C@@H]5/C=C\[C@@H]4O
InChI InChI=1S/C19H21NO4/c1-9(21)10-8-15(23)17-16-11(10)7-13-12-3-4-14(22)18(24-17)19(12,16)5-6-20(13)2/h3-4,8,12-14,18,22-23H,5-7H2,1-2H3/t12-,13+,14-,18-,19-/m0/s1 N Key:DUAISAINBBQDAF-LEPYJNQMSA-N N
N (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).

6-MAM is rapidly created from heroin in the body, and then is either metabolized into morphine or excreted in the urine. 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. 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.

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 which is 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 of sorts for the systemic delivery of morphine, which actively binds with μ-opioid receptors.

Black tar heroin

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-monoacetylmorphine somewhat more potent than heroin, but it is rarely encountered as an illicit drug due to the difficulty in selectively acetylating morphine at the 6-position without also acetylating the 3-position. This can however be accomplished by using acetic acid with an appropriate catalyst to carry out the acetylation,{[1]} rather than acetic anhydride, as acetic acid is not a strong enough acetylating agent to acetylate the phenolic 3-hydroxy group but is able to acetylate the 6-hydroxy group, thus selectively producing 6-MAM rather than heroin. The process used in creating black tar heroin actually leaves 6-MAM in the final product, which is one of several reasons why black tar, even when less pure, may be more potent than some powder varieties of heroin.

See also

• 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

UpToDate Contents

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• 1. オピオイド使用障害：疫学、薬理学、臨床症状、経過、スクリーニング、評価、および診断 opioid use disorder epidemiology pharmacology clinical manifestations course screening assessment and diagnosis

English Journal

• Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine.

• Silva-Torres LA1, Vélez C2, Lyvia Alvarez J3, Ortiz JG4, Zayas B5.
• Toxicology in vitro : an international journal published in association with BIBRA.Toxicol In Vitro.2014 Oct;28(7):1312-1319. doi: 10.1016/j.tiv.2014.06.013. Epub 2014 Jul 8.
• The use of xylazine as a drug of abuse has emerged worldwide in the last 7years, including Puerto Rico. Clinical findings reported that xylazine users present greater physiological deterioration, than heroin users. The aim of this study was to assess the xylazine toxicity on endothelial cells, as th
• PMID 25017475

• Role of 6-monoacetylmorphine in the acute release of striatal dopamine induced by intravenous heroin.

• Gottås A, Boix F, Oiestad EL, Vindenes V, Mørland J.
• The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP).Int J Neuropsychopharmacol.2014 Sep;17(9):1357-65. doi: 10.1017/S1461145714000169. Epub 2014 Feb 27.
• After injection, heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM) and further to morphine. As morphine has been shown to increase striatal dopamine, whereas 6-MAM has not been studied in this respect, we gave i.v. injections of 3 μmol 6-MAM, morphine or heroin to rats. Opioids were me
• PMID 24576415

• Underrepresentation of Heroin Involvement in Unintentional Drug Overdose Deaths in Allegheny County, PA.

• Mertz KJ1, Janssen JK, Williams KE.
• Journal of forensic sciences.J Forensic Sci.2014 Jul 16. doi: 10.1111/1556-4029.12541. [Epub ahead of print]
• Drugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of "morphine" and "codeine" listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewe
• PMID 25041514

Japanese Journal

• Methadone and Heroin Antinociception: Predominant δ-Opioid-Receptor Responses in Methadone-Tolerant Mice

• The Japanese journal of pharmacology 88(3), 319-331, 2002-03-01
• NAID 10008187965

• Concentrations of morphine and codeine in urine of heroin abusers

• Legal medicine 1(3), 140-144, 1999-09-01
• NAID 10013629093

• Heroin Antinociception Changed From Mu to Delta Receptor in Streptozotocin-Treated Mice

• The Japanese journal of pharmacology 78(4), 443-454, 1998-12-01
• NAID 10008681706

Related Links

• 6-Monoacetylmorphine - Wikipedia, the free encyclopedia

6-Monoacetylmorphine (6-MAM) or 6-acetylmorphine is one of three active metabolites of heroin (diacetylmorphine), ... at the 3-position in order to be bioactivated; this makes 6-monoacetylmorphine somewhat more potent than heroin, but it is ...

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