6-Monoacetylmorphine

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.

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 prodrug, 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.

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.

Synthesis

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 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 opioids such as codeine, morphine sulfate, and heroin. Trace amounts of 6-MAM are excreted approximately 6–8 hours following heroin use.

6-MAM is naturally found in trace amounts in rat and cow brains.

References

References

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2. "Pagina di transizione".
3. (1984). "Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine". Progress in Neuro-Psychopharmacology & Biological Psychiatry.
4. (December 2020). "What the lab can and cannot do: clinical interpretation of drug testing results". Critical Reviews in Clinical Laboratory Sciences.
5. (July 1988). "6-Acetylmorphine: a natural product present in mammalian brain". Proceedings of the National Academy of Sciences of the United States of America.