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
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
DescriptionCurator'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
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL233 |
10.3 nM [EC50] | ||
Target ID: CHEMBL240 |
2.2 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | ORLAAM Approved UseORLAAM 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 Date7.42176E11 |
PubMed
Title | Date | PubMed |
---|---|---|
Metabolism of levo-alpha-Acetylmethadol (LAAM) by human liver cytochrome P450: involvement of CYP3A4 characterized by atypical kinetics with two binding sites. | 2001 Apr |
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History and current status of opioid maintenance treatments: blending conference session. | 2002 Sep |
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Torsade de pointes associated with very-high-dose methadone. | 2002 Sep 17 |
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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 |
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Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsade de pointes. | 2005 Apr |
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Torsades de pointes with methadone. | 2005 Apr |
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Medication development for addictive disorders: the state of the science. | 2005 Aug |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone. | 2006 Sep |
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Substitution treatment for opioid addicts in Germany. | 2007 Feb 2 |
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In silico prediction of pregnane X receptor activators by machine learning approaches. | 2007 Jan |
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Dialectical behavior therapy for substance abusers. | 2008 Jun |
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Stereoselective Inhibition of the hERG1 Potassium Channel. | 2010 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9360954
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
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C67413
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EMA ASSESSMENT REPORTS |
ORLAAM (WITHDRAWN: OPIOID-RELATED DISORDERS)
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WHO-ATC |
N07BC03
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DEA NO. |
9648
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WHO-VATC |
QN07BC03
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SUB08451MIG
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m6789
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LEVACETYLMETHADOL
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CHEMBL1514
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R3B637Y991
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C87359
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1571
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DTXSID3023211
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15130
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1477-40-3
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100000085464
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3175
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DB01227
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34433-66-4
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6441
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7212
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)