Monoacetylmorphine
Encyclopedia
6-Monoacetylmorphine or 6-Acetylmorphine is one of three active metabolite
s 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. 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, 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 receptor
s because the 3-hydroxy group which is essential for effective binding to the receptor is masked by the acetyl group. Therefore, heroin is simply a pro-drug, serving as a lipophilic transporter of sorts for the sysemic delivery of 6-monoacetylmorphine, morphine and other metabolites, which actively bind with μ-opioid receptors.
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, 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 reason why black tar can be less refined, but at the same time more potent than powder varieties of heroin.
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s of heroin (diacetylmorphine), the others being morphine and the much less active 3-Monoacetylmorphine
3-Monoacetylmorphine
3-Monoacetylmorphine or 3-acetylmorphine is less active metabolite of heroin , the other two being morphine and more active 6-monoacetylmorphine ....
(3-MAM).
6-MAM is rapidly created from heroin in the body, and then is either metabolized into morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
or excreted in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. Since 6-MAM is a unique metabolite to heroin, its presence in the urine confirms that heroin was the opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
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
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, morphine sulfate, 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, 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 receptor
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
s because the 3-hydroxy group which is essential for effective binding to the receptor is masked by the acetyl group. Therefore, heroin is simply a pro-drug, serving as a lipophilic transporter of sorts for the sysemic delivery of 6-monoacetylmorphine, morphine and other metabolites, which actively bind with μ-opioid receptors.
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
with an appropriate catalyst to carry out the acetylation
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
, rather than acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
, 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
Black tar heroin
Black tar heroin is a type of illicit opiate narcotic drug formed from the incomplete acetylation of morphine. It is also called brown.Black tar can contain a variable percentage of heroin, but despite the name, what makes Black Tar specific as a type is not actually its heroin content, but rather...
actually leaves 6-MAM in the final product, which is one reason why black tar can be less refined, but at the same time more potent than powder varieties of heroin.
See also
- M3GMorphine-3-glucuronideMorphine-3-glucuronide is a metabolite of morphine produced by UGT2B7. It is not active as an opioid agonist, but does have some action as a convulsant, which does not appear to be mediated through opioid receptors; it is mediated by GABA/glycinergic system...
, Morphine-3-glucuronide an inactive metabolite of morphine much as 3MAM is the inactive metabolite of heroin (notably here as morphine is the active metabolite of heroin itself with this chemical of this article subject being the intermediate stage) - M6GMorphine-6-glucuronideMorphine-6-glucuronide is a major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine . M6G is formed from morphine by the enzyme UDP-Glucuronosyltransferase-2B7...
, 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 (3MAM) of a parent compound (heroin) of this article's chemical