Levacetylmethadol ( INN), levomethadyl acetate ( USAN), OrLAAM (trade name) or levo-α-acetylmethadol (LAAM) is a synthetic

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

similar in structure to methadone. It has a long duration of action due to its active metabolites.

Medical uses

LAAM is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone or buprenorphine. LAAM is used as an

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solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Solutio ...

of LAAM hydrochloride at a concentration of 10 mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with methadone is 20–40 mg. The first dose for patients who have been receiving methadone will be a little higher than the amount of methadone that was being taken every day, but not more than 120 mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered two to three times a week.

Pharmacology

Pharmacodynamics

LAAM acts as a

μ-opioid receptor The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical ...

agonist. It also acts as a potent, noncompetitive α₃β₄ neuronal nicotinic acetylcholine receptor antagonist.

Pharmacokinetics

LAAM undergoes extensive first-pass metabolism to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These metabolites are more potent than the parent drug.

Chemistry

LAAM, or levomethadyl acetate, is the ''levo'' isomer of

acetylmethadol Acetylmethadol, also known as methadyl acetate, is a synthetic opioid analgesic. It is a racemic mixture of alphacetylmethadol (α-acetylmethadol) and betacetylmethadol (β-acetylmethadol), which are in turn racemic mixtures of levacetylmetha ...

, or α-methadyl acetate. The ''dextro'' isomer, ''d''- alphacetylmethadol (''d''-α-acetylmethadol), is more potent but shorter acting. The ''levo'' isomer is also less toxic with an in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed to s of 61 mg/kg s.c. and 118.3 mg/kg orally for ''dl''-α-methadyl acetate. It has a

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depen ...

of 215 °C and a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...

of 353.50. β-methadyl acetate also exists, however it is more

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a sub ...

and less active than α-methadyl acetate and has no current medical use.

History

LAAM was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence. In 2001, LAAM was removed from the European market due to reports of life-threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.

Society and culture

Legal status

Before August 1993, LAAM was classified as a schedule I drug in the United States. LAAM is not approved for use in

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and

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by to ...

. At present, it is a Schedule II Narcotic controlled substance in the United States with a DEA ACSCN of 9648 and a national aggregate annual manufacturing quota of 4 grammes as of 2013.

References

External links

* * * {{Opioid receptor modulators Acetate esters Enantiopure drugs Dimethylamino compounds HERG blocker Mu-opioid receptor agonists Nicotinic antagonists Synthetic opioids