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| Trade names | OrLAAM |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Protein binding | ~80% |
| Metabolism | CYP3A4 |
| Eliminationhalf-life | 2.6 days |
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| Chemical and physical data | |
| Formula | C23H31NO2 |
| Molar mass | 353.506 g·mol−1 |
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Levacetylmethadol (INN),levomethadyl acetate (USAN),OrLAAM (trade name) or levo-α-acetylmethadol (LAAM)[1][2] is a syntheticopioid similar in structure tomethadone. It has a long duration of action due to its activemetabolites.
LAAM is indicated as a second-line treatment for the treatment and management ofopioid dependence if patients fail to respond to drugs likemethadone orbuprenorphine.
LAAM is used as anoralsolution of LAAMhydrochloride 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 withmethadone is 20–40 mg. The first dose for patients who have been receivingmethadone 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.
LAAM acts as aμ-opioid receptoragonist. It also acts as a potent,noncompetitiveα3β4 neuronalnicotinic acetylcholine receptorantagonist.[3]
LAAM undergoes extensivefirst-pass metabolism to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. Thesemetabolites are more potent than the parent drug.
LAAM, or levomethadyl acetate, is thelevo isomer ofacetylmethadol, or α-methadyl acetate. Thedextro isomer,d-alphacetylmethadol (d-α-acetylmethadol), is more potent but shorter acting. Thelevo isomer is also less toxic with anLD50 in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed toLD50s of 61 mg/kg s.c. and 118.3 mg/kg orally fordl-α-methadyl acetate. It has amelting point of 215 °C and amolecular weight of 353.50. β-methadyl acetate also exists, but is moretoxic and less active than α-methadyl acetate and has no current medical use.
LAAM was approved in 1993 by theU.S. Food and Drug Administration for use in the treatment ofopioid dependence. In 2001, LAAM was removed from the European market due to reports of life-threateningventricular rhythm disorders.[4] In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.[5]
Before August 1993, LAAM was classified as aschedule I drug in the United States. LAAM is not approved for use inAustralia andCanada. 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 grams as of 2013.[needs update]
