6-MAM

6-Monoacetylmorphine

Clinical data
Routes of administration	Intravenous
ATC code	none
Legal status
Legal status	AU: S9 (Prohibited) UK: Class A US: Schedule I
Pharmacokinetic data
Biological half-life	< 5 mins
Identifiers
IUPAC name 3-hydroxy-6-acetyl-(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan
Synonyms	6-acetylmorphine
CAS Number	2784-73-8 N
PubChem (CID)	5462507
ChemSpider	4575434 Y
ChEMBL	CHEMBL592009 Y
ECHA InfoCard	100.150.555
Chemical and physical data
Formula	C19H21NO4
Molar mass	327.374 g/mol
3D model (Jmol)	Interactive image
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
NY (what is this?)

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 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.

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.

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.

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, 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.