6-Monoacetylmorphine

"6-AM" redirects here. For other uses, see 6AM.

6-Monoacetylmorphine

Clinical data
Trade names	6-Monoacetylmorphine
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	0.6 hours
Identifiers
IUPAC name (9-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl) acetate
CAS Number	2784-73-8  Y
PubChem CID	5462507
DrugBank	DBMET01172  Y
ChemSpider	4575434  Y
UNII	M5E47P1ZCH
ChEBI	CHEBI:2168  Y
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 [H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2OC(C)=O
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 Y[ drugbank ] Key:JJGYGPZNTOPXGV-SSTWWWIQSA-N Y[ drugbank ]
NY  (what is this?)    (verify)

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).

Pharmacology

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]}

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-MAM somewhat more potent than heroin. ^[3]

Availability

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]

Synthesis

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 concentrated sulfuric acid 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

Detection in bodily fluids

Since 6-MAM is a metabolite unique to heroin, its presence in the urine confirms heroin use. This is significant because a urine immunoassay drug screen 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 are excreted approximately 6–8 hours following heroin use.^{[ citation needed ]}

6-MAM is naturally found in trace amounts in rat and cow brains. ^[5]

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

1. Inturrisi CE, Schultz M, Shin S, Umans JG, Angel L, Simon EJ (1983). "Evidence from opiate binding studies that heroin acts through its metabolites". Life Sciences. 33 (Suppl 1): 773–6. doi:10.1016/0024-3205(83)90616-1. PMID   6319928.
2. "Pagina di transizione". www.researchitaly.it.
3. Tasker RA, Vander Velden PL, Nakatsu K (1984). "Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 8 (4–6): 747–50. doi:10.1016/0278-5846(84)90051-4. PMID   6543399. S2CID   23566872.
4. Kapur BM, Aleksa K (December 2020). "What the lab can and cannot do: clinical interpretation of drug testing results". Critical Reviews in Clinical Laboratory Sciences. 57 (8): 548–585. doi: 10.1080/10408363.2020.1774493 . PMID   32609540.
5. Weitz CJ, Lowney LI, Faull KF, Feistner G, Goldstein A (July 1988). "6-Acetylmorphine: a natural product present in mammalian brain". Proceedings of the National Academy of Sciences of the United States of America. 85 (14): 5335–8. Bibcode:1988PNAS...85.5335W. doi: 10.1073/pnas.85.14.5335 . PMC   281745 . PMID   3393541.