6-Monoacetylmorphine
- none
- 3-Hydroxy-6-acetyl-(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan
- 2784-73-8 N
- 5462507
- 4575434 Y
- M5E47P1ZCH
- ChEMBL592009 Y
- DTXSID60182154
- Interactive image
- CC(=O)O[C@H]1/C=C\[C@H]2[C@H]3Cc4ccc(O)c5O[C@@H]1[C@]2(CCN3C)c45
- 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
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]
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 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.
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.[5]
6-MAM is naturally found in trace amounts in rat and cow brains. [6]
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
References
- ^ 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.
- ^ "Pagina di transizione". www.researchitaly.it.
- ^ 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.
- ^ 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.
- ^ "Opiates | Drug Info | Resources | Redwood Toxicology Laboratory". www.redwoodtoxicology.com.
- ^ 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.
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Antagonists |
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- Enkephalinase inhibitors: Amastatin
- BL-2401
- Candoxatril
- D -Phenylalanine
- Dexecadotril (retorphan)
- Ecadotril (sinorphan)
- Kelatorphan
- Racecadotril (acetorphan)
- RB-101
- RB-120
- RB-3007
- Opiorphan
- Selank
- Semax
- Spinorphin
- Thiorphan
- Tynorphin
- Ubenimex (bestatin)
- Propeptides: β-Lipotropin (proendorphin)
- Prodynorphin
- Proenkephalin
- Pronociceptin
- Proopiomelanocortin (POMC)
- Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)