Monoacetylmorphine

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Monoacetylmorphine
Systematic (IUPAC) name
3-hydroxy-6-acetyl-(5α,6α)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan
Identifiers
CAS number	2784-73-8
ATC code	?
PubChem	5462507
Chemical data
Formula	C19H21NO4
Mol. mass	327.374 g/mol
Synonyms	Monoacetylmorphine, 6-acetylmorphine
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Schedule I(US)
Routes	Intravenous

6-monoacetylmorphine (6-MAM) is one of 2 active metabolites of heroin (diacetylmorphine), the other being the much less active 3-monoacetylmorphine (3-MAM).

Along with morphine, 6-MAM is rapidly created from heroin in the body, and is excreted in the urine. Since 6-MAM is a unique metabolite to heroin, its presence in the urine confirms that heroin was the opiate 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 such as codeine, morphine sulphate, and heroin. 6-MAM remains in the urine for no more than 24 hours so a urine specimen must be collected soon after the last heroin use, but the presence of 6-MAM guarantees that heroin was in fact used as recently as within the last day. 6-MAM is naturally found in the brain,^[1] but in such small quantities that detection of this compound in urine virtually guarantees that heroin has been recently been consumed.

In contrast to heroin, 6-MAM actively binds with μ-opioid receptors; diacetylmorphine (heroin) itself actually has very weak affinity to μ-opioid receptors because the 3-hydroxy group which is essential for binding to the receptor is masked by the acetyl group, however heroin is rapidly metabolised by esterase enzymes in the brain, giving it an extremely short half life. The high lipid solubility of heroin causes its powerful effects, because it delivers a higher concentration of morphine past the blood brain barrier much quicker then morphine alone.^[2]

6-monoacetylmorphine 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 3-position in order to be bioactivated; this makes 6-monoacetylmorphine somewhat more potent than heroin,^[3] 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.

[edit] References

1. ^ Weitz CJ, Lowney LI, Faull KF, Feistner G, Goldstein A. 6-Acetylmorphine: a natural product present in mammalian brain. Proceedings of the National Academy of Science U S A. 1988 Jul;85(14):5335-8.
2. ^ Inturrisi CE, Schultz M, Shin S, Umans JG, Angel L, Simon EJ. Evidence from opiate binding studies that heroin acts through its metabolites. Life Sciences. 1983;33 Suppl 1:773-6.
3. ^ Tasker RA, Vander Velden PL, Nakatsu K. Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine. Progress in Neuropsychopharmacology and Biological Psychiatry. 1984;8(4-6):747-50.