U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H31NO2
Molecular Weight 353.4977
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOMETHADYL ACETATE

SMILES

CC[C@H](OC(C)=O)C(C[C@H](C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2

InChI

InChIKey=XBMIVRRWGCYBTQ-AVRDEDQJSA-N
InChI=1S/C23H31NO2/c1-6-22(26-19(3)25)23(17-18(2)24(4)5,20-13-9-7-10-14-20)21-15-11-8-12-16-21/h7-16,18,22H,6,17H2,1-5H3/t18-,22-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://apps.who.int/medicinedocs/en/d/Js4956e/4.4.html | https://www.ncbi.nlm.nih.gov/pubmed/9437627

Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits.

Originator

Sources: Pohland et al., J. Am. Chem. Soc. 71, 460 (1949)
Curator's Comment: http://www.drugfuture.com/chemdata/levomethadyl-acetate.html | http://www.druglead.com/cds/levomethadyl-acetate.html

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ORLAAM

Approved Use

ORLAAM is indicated for the management of opiate dependence. ORLAAM should be reserved for the use in treatment of opiate-addicted patients who fail to show an acceptable response to other adequate treatments for opiate addiction, either because of insufficient effectiveness or the inability to achieve effective dose due to intolerable adverse effects from those drugs

Launch Date

1993
PubMed

PubMed

TitleDatePubMed
Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM).
2001
Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation.
2001 Sep
Torsade de pointes associated with very-high-dose methadone.
2002 Sep 17
Practical considerations for the clinical use of buprenorphine.
2004 Aug
Treating opioid dependence. Growing implications for primary care.
2004 Feb 9
Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies.
2005
Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsade de pointes.
2005 Apr
Torsades de pointes with methadone.
2005 Apr
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Blood-brain equilibration kinetics of levo-alpha-acetyl-methadol using a chronically instrumented sheep preparation.
2006 Jan
HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone.
2006 Sep
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.
2007
QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.
2007 Dec 10
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Pharmacokinetic drug interactions of synthetic opiate analgesics.
2009 Mar-Apr
The use of driving impairing medicines: a European survey.
2009 Nov
Patents

Sample Use Guides

The initial dose of levomethadyl hydrochloride acetate (ORLAAM) for street addicts should be 20 to 40 mg. Each subsequent dose, administered at 48- or 72-hour intervals, may be adjusted in increments of 5 to 10 mg until a pharmacokinetic and pharmacodynamic steady-state is reached, usually within 1 or 2 weeks
Route of Administration: Oral
In Vitro Use Guide
Levomethadyl acetate (LAAM) exerts a concentration-dependent effect on mu opioid receptor phosphorylation in CHO cells. Significant agonist-induced receptor phosphorylation enhancements were observed at concentrations as low as 100 nM for LAAM
Name Type Language
LEVOMETHADYL ACETATE
MI   USAN  
USAN  
Official Name English
(-)-6-(DIMETHYLAMINO)-4,4-DIPHENYL-3-HEPTANOL ACETATE (ESTER)
Common Name English
LAAM
Code English
levacetylmethadol [INN]
Common Name English
LEVOACETYL METHADOL
Common Name English
(1S,4S)-(6-DIMETHYLAMINO-4,4-DIPHENYL-HEPTAN-3-YL) ACETATE
Common Name English
LAA-M
Code English
LEVACETYLMETHADOL [EMA EPAR]
Common Name English
LEVACETYLMETHADOL
EMA EPAR   INN   MART.   WHO-DD  
INN  
Official Name English
LEVOMETHADYL ACETATE [USAN]
Common Name English
LEVACETYLMETHADOL [MART.]
Common Name English
Levacetylmethadol [WHO-DD]
Common Name English
BENZENEETHANOL, .BETA.-(2-(DIMETHYLAMINO)PROPYL)-.ALPHA.-ETHYL-.BETA.-PHENYL-, ACETATE (ESTER), (-)-
Common Name English
LEVOMETHADYL ACETATE [MI]
Common Name English
LEVO-ALPHACETYLMETHADOL
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67413
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
EMA ASSESSMENT REPORTS ORLAAM (WITHDRAWN: OPIOID-RELATED DISORDERS)
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
WHO-ATC N07BC03
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
DEA NO. 9648
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
WHO-VATC QN07BC03
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
Code System Code Type Description
EVMPD
SUB08451MIG
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
MERCK INDEX
m6789
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
LEVACETYLMETHADOL
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
ChEMBL
CHEMBL1514
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PRIMARY
FDA UNII
R3B637Y991
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PRIMARY
NCI_THESAURUS
C87359
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PRIMARY
DRUG CENTRAL
1571
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PRIMARY
EPA CompTox
DTXSID3023211
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PRIMARY
PUBCHEM
15130
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
CAS
1477-40-3
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
SMS_ID
100000085464
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
INN
3175
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PRIMARY
DRUG BANK
DB01227
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PRIMARY
CAS
34433-66-4
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
SUPERSEDED
CHEBI
6441
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY
IUPHAR
7212
Created by admin on Sat Dec 16 17:02:38 GMT 2023 , Edited by admin on Sat Dec 16 17:02:38 GMT 2023
PRIMARY