Levomethadyl acetate

drugbox
IUPAC_name = (6-dimethylamino-4,4-diphenyl-heptan-3-yl) acetate


width = 140
CAS_number = 509-74-0
ATC_prefix =
ATC_suffix =
PubChem = 15130
DrugBank = APRD00745
C = 23 | H = 31 | N = 1 | O = 2
molecular_weight = 353.50
bioavailability =
protein_bound = ~80%
metabolism = CYP3A4
elimination_half-life = 2.6 days
excretion =
pregnancy_AU =
pregnancy_US =
pregnancy_category =
legal_AU = ?
legal_CA = Schedule I
legal_UK = ?
legal_US = Schedule II
legal_status =
routes_of_administration = Oral

Levomethadyl acetate, also known as 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. It was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence. In 2001, the product ORLAAM was removed from the European market due to reports of severe cardiac-related adverse events. In 2003, Roxane Laboratories, Inc. discontinued ORLAAM in the US. [ [http://www.fda.gov/cder/drug/shortages/orlaam.htm Drug Shortage: Drug to be Discontinued ] ]

Indications

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 not approved for use in Canada.

Chemistry and Pharmacology

Levomethadyl acetate is the "levo" isomer of α-methadyl acetate. The "dextro" isomer is more potent but shorter acting. The "levo" isomer is also less toxic with an LD50 in mice of 110mg/kg s.c. and 172.8mg/kg orally as opposed to LD50s of 61mg/kg s.c. and 118.3mg/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.

Levomethadyl acetate 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.

Dosing

LAAM is used as an oral solution of levomethadyl acetate hydrochloride at a concentration of 10mg/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 20-40mg. 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 three times a week.

References

External links

* [http://www.drugs.com/cons/levomethadyl.html LAAM Drug Information]
* [http://www.rxlist.com/cgi/generic2/levomethadyl_wcp.htm RxList Monograph for Orlaam]
* [http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00745.txt DrugBank: Levomethadyl Acetate]
* http://cat.inist.fr/?aModele=afficheN&cpsidt=2706063
* http://cat.inist.fr/?aModele=afficheN&cpsidt=2390242