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

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

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

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

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 levacetylmeth ...

, 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 of 215 °C and a molecular weight of 353.50. β-methadyl acetate also exists, however it is more toxic 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

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

and Canada. 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