Levacetylmethadol
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| Trade names | OrLAAM |
| Routes of administration | By mouth |
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| Pharmacokineticdata | |
| Protein binding | ~80% |
| Metabolism | CYP3A4 |
| Eliminationhalf-life | 2.6 days |
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| Chemical and physical data | |
| Formula | C23H31NO2 |
| Molar mass | 353.506g·mol−1 |
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Levacetylmethadol(INN),levomethadyl acetate(USAN),OrLAAM(trade name) or levo-α-acetylmethadol (LAAM)[1][2]is a syntheticopioidsimilar in structure tomethadone.It has a long duration of action due to its activemetabolites.
Medical uses[edit]
LAAM is indicated as a second-line treatment for the treatment and management ofopioid dependenceif patients fail to respond to drugs likemethadoneorbuprenorphine.
LAAM is used as anoralsolutionof LAAMhydrochlorideat 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 withmethadoneis 20–40 mg. The first dose for patients who have been receivingmethadonewill 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[edit]
Pharmacodynamics[edit]
LAAM acts as aμ-opioid receptoragonist.
It also acts as a potent,noncompetitiveα3β4neuronalnicotinic acetylcholine receptorantagonist.[3]
Pharmacokinetics[edit]
LAAM undergoes extensivefirst-pass metabolismto the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. Thesemetabolitesare more potent than the parent drug.
Chemistry[edit]
LAAM, or levomethadyl acetate, is thelevoisomer ofacetylmethadol,or α-methadyl acetate. Thedextroisomer,d-alphacetylmethadol(d-α-acetylmethadol), is more potent but shorter acting. Thelevoisomer is also less toxic with anLD50in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed toLD50sof 61 mg/kg s.c. and 118.3 mg/kg orally fordl-α-methadyl acetate. It has amelting pointof 215 °C and amolecular weightof 353.50. β-methadyl acetate also exists, however it is moretoxicand less active than α-methadyl acetate and has no current medical use.
History[edit]
LAAM was approved in 1993 by theU.S. Food and Drug Administrationfor 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]
Society and culture[edit]
Legal status[edit]
Before August 1993, LAAM was classified as aschedule Idrug in the United States. LAAM is not approved for use inAustraliaandCanada.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[edit]
- ^US 3021360,Pholand A, "3-Acetoxy-4,4-diphenyl-6-methylaminoheptane", issued 12 February 1962, assigned to Eli Lilly and Company
- ^US 2565592,Clark RL, "Alpha-d1-4-acetoxy-1-methyl-3,3-diphenylhexylamine and salts", issued 28 August 1951, assigned to Merck & Company
- ^Xiao Y, Smith RD, Caruso FS, Kellar KJ (October 2001)."Blockade of rat α3β4 nicotinic receptor function by methadone, its metabolites, and structural analogs".The Journal of Pharmacology and Experimental Therapeutics.299(1): 366–71.PMID11561100.
- ^"EMEA Public Statement on the Recommendation to Suspend the Marketing Authorisation for Orlaam (Levacetylmethadol) in the European Union"(PDF).The European Agency for the Evaluation of Medicinal Products.19 April 2001.
- ^"Orlaam (levomethadyl acetate hydrochloride)".US FDA Safety Alerts.20 August 2013. Archived fromthe originalon 10 October 2013.
Further reading[edit]
- Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML, Johnson RE (June 1997). "Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial".JAMA.277(24): 1945–51.doi:10.1001/jama.1997.03540480045037.PMID9200635.
- Jones HE, Strain EC, Bigelow GE, Walsh SL, Stitzer ML, Eissenberg T, Johnson RE (August 1998)."Induction with levomethadyl acetate: safety and efficacy".Archives of General Psychiatry.55(8): 729–36.doi:10.1001/archpsyc.55.8.729.PMID9707384.
External links[edit]
- "LAAM Drug Information".Drugs.com.
- "Monograph for Orlaam".RxList.Archived fromthe originalon 2008-07-19.
- "Levomethadyl Acetate".DrugBank.