6-Monoacetylmorphine
 | |
| Systematic (IUPAC) name | |
|---|---|
|
3-hydroxy-6-acetyl-(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan | |
| Clinical data | |
| Routes of administration | Intravenous |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Biological half-life | < 5 mins |
| Identifiers | |
| CAS Number |
2784-73-8  |
| ATC code | none |
| PubChem | CID 5462507 |
| ChemSpider |
4575434  |
| ChEMBL |
CHEMBL592009 |
| Synonyms | 6-acetylmorphine |
| Chemical data | |
| Formula | C19H21NO4 |
| Molar mass | 327.374 g/mol |
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| (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.[1] 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.[2]
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.[3][4]
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,[5] 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,{} 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. 6MAM can also be synthesized from morphine using glacial acetic acid 99%. It is only strong enough to acetylate the hydroxyl group at the 6th position only. Thus no diacetylmorphine is created, as well as 3MAM which is a weak byproduct using either acetic anhydride or acetyl chloride. Either of those acids are strong enough to modify the morphine molecule. Acetic acid, on the other hand is only strong enough to acetylate the 6th position. Therefore only creating 6-Monoacetylmorphine. 6MAM does not have to undergo deacetylation to become active like diacetylmorphine does. 6MAM is therefore more active than that of diacetylmorphine. And 3MAM is either less potent than morphine or a similar potency to morphine. Therefore glacial acetic acid 99% is the more ideal way as well as the cheapest way to create the strongest form of heroin metabolite. Acetic acid also is not a watched chemical and is common in cleaning agents as well as gardening supplies. The purity of the acetic acid being used is very important however. It must be of high purity (97-99 percent) for the acid to properly acetylate the morphine at the 6th position effectively creating 6MAM. 6MAM is approximately 30 percent more active than diacetylmorphine itself. This is why black tar heroin is generally more potent when the purity is similar. Black tar heroin is acetylated with acetic acid, thus only creating 6MAM. 40 percent afghan heroin is equal to about 30 percent purity black tar. Most black tar heroin is between 55 and 93 percent purity. In black tar heroin the morphine is concentrated in liquid opium to approximately 90 percent purity. Instead of extracting the morphine from the opium, it is instead concentrated within the opium sap and acetylated as is. This is what gives it that gummy appearance. It is more or less concentrated and acetylated opium. Acetic acid is used and therefore only makes 6MAM. This is why black tar heroin by many is preferred, because the active drug has a 30 percent higher potency overall.
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
- ↑ https://www.redwoodtoxicology.com/resources/drug_info/opiates
- ↑ "6-Acetylmorphine: a natural product present in mammalian brain". Proc. Natl. Acad. Sci. U.S.A. 85 (14): 5335–8. July 1988. doi:10.1073/pnas.85.14.5335. PMC 281745. PMID 3393541.
- ↑ "Evidence from opiate binding studies that heroin acts through its metabolites". Life Sci. 33 Suppl 1: 773–6. 1983. doi:10.1016/0024-3205(83)90616-1. PMID 6319928.
- ↑ Ricerca Italiana - PRIN - Role of morphine glucuronides in heroin addiction
- ↑ "Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine". Prog. Neuropsychopharmacol. Biol. Psychiatry 8 (4-6): 747–50. 1984. doi:10.1016/0278-5846(84)90051-4. PMID 6543399.