6-Monoacetylmorphine

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. 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, but in such small quantities that detection of this compound in urine virtually guarantees that heroin has recently been consumed.

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.



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, 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.