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

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6-Monoacetylmorphine

Clinical data
Other names	6-acetylmorphine
Routes of administration	Intravenous
ATC code	none
Legal status
Legal status	AU: S9 (Prohibited substance) UK: Class A
Pharmacokinetic data
Elimination half-life	< 5 mins
Identifiers
IUPAC name 3-Hydroxy-6-acetyl-(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan
CAS Number	2784-73-8 N
PubChem CID	5462507
ChemSpider	4575434 Y
UNII	M5E47P1ZCH
ChEMBL	ChEMBL592009 Y
CompTox Dashboard (EPA)	DTXSID60182154
ECHA InfoCard	100.150.555
Chemical and physical data
Formula	C19H21NO4
Molar mass	327.380 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(=O)O[C@H]1/C=C\[C@H]2[C@H]3Cc4ccc(O)c5O[C@@H]1[C@]2(CCN3C)c45
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
NY (what is this?)  (verify)

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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.^{[citation needed]}

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]

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 along with heroin itself.^[4]

The production of black tar heroin results in significant amounts of 6-MAM in the final product.^{[citation needed]} 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.

• 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