You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:41:28 UTC
HMDB IDHMDB0015358
Secondary Accession Numbers
  • HMDB15358
Metabolite Identification
Common NameLevomethadyl Acetate
DescriptionLevomethadyl Acetate is only found in individuals that have used or taken this drug. It is a narcotic analgesic with a long onset and duration of action. It is used mainly in the treatment of narcotic dependence. [PubChem]Opiate receptors (Mu, Kappa, Delta) are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Levomethadyl acetate effectively opens calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist), resulting in hyperpolarization and reduced neuronal excitability.
Structure
Data?1582753288
Synonyms
ValueSource
(-)-alpha-AcetylmethadolChEBI
(1S,4S)-4-(Dimethylamino)-1-ethyl-2,2-diphenylpentyl acetateChEBI
1-alpha-AcetylmethadolChEBI
LAAMChEBI
LevacetilmetadolChEBI
LevacetylmethadolumChEBI
LevomethadylChEBI
OrlaamChEBI
LevacetylmethadolKegg
(-)-a-AcetylmethadolGenerator
(-)-Α-acetylmethadolGenerator
(1S,4S)-4-(Dimethylamino)-1-ethyl-2,2-diphenylpentyl acetic acidGenerator
1-a-AcetylmethadolGenerator
1-Α-acetylmethadolGenerator
Levomethadyl acetic acidGenerator
Levo-alphacetylmethadolHMDB
Levo-methadyl acetateHMDB
Nor-laamHMDB
Levo-alpha-acetylmethadolHMDB
Levomethadyl acetate hydrochlorideHMDB
(3R,6R)-3-Acetoxy-6-dimethylamino-4,4-diphenylheptaneHMDB
DimepheptanolHMDB
6-(Dimethylamino)-4,4-diphenyl-3-heptanol acetateHMDB
AlphacetylmethadolHMDB
LevoacetylmethadolHMDB
MethadolHMDB
AcetylmethadolHMDB
AmidolacetateHMDB
AcemethadoneHMDB
Levo alpha acetylmethadolHMDB
Methadyl acetateHMDB
Chemical FormulaC23H31NO2
Average Molecular Weight353.4977
Monoisotopic Molecular Weight353.235479241
IUPAC Name(3S,6S)-6-(dimethylamino)-4,4-diphenylheptan-3-yl acetate
Traditional Namelevomethadyl acetate
CAS Registry Number1477-40-3
SMILES
CC[C@H](OC(C)=O)C(C[C@H](C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1
InChI Identifier
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
InChI KeyXBMIVRRWGCYBTQ-AVRDEDQJSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Aralkylamine
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Amine
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0018 g/LNot Available
LogP5.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0018 g/LALOGPS
logP4.78ALOGPS
logP4.88ChemAxon
logS-5.3ALOGPS
pKa (Strongest Basic)9.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area29.54 ŲChemAxon
Rotatable Bond Count9ChemAxon
Refractivity117.86 m³·mol⁻¹ChemAxon
Polarizability40.53 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0uk9-9081000000-c21fec0e8e70744482b4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0029000000-c28a76d17f554d7ba439Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-022c-7096000000-e5337d3be9cfb3f23f09Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fkc-5190000000-113274c2b46b6767d5b3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-1019000000-248c95ec24dae3299384Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0nmi-4039000000-abf719229500214241e6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-9081000000-e357c686965cbd06e26cSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01227 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01227 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01227
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID14401
KEGG Compound IDC08012
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevomethadyl_Acetate
METLIN IDNot Available
PubChem Compound15130
PDB IDNot Available
ChEBI ID6441
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE: A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000 Nov 2;343(18):1290-7. [PubMed:11058673 ]
  2. Kreek MJ, Vocci FJ: History and current status of opioid maintenance treatments: blending conference session. J Subst Abuse Treat. 2002 Sep;23(2):93-105. [PubMed:12220607 ]
  3. Kuo I, Brady J, Butler C, Schwartz R, Brooner R, Vlahov D, Strathdee SA: Feasibility of referring drug users from a needle exchange program into an addiction treatment program: experience with a mobile treatment van and LAAM maintenance. J Subst Abuse Treat. 2003 Jan;24(1):67-74. [PubMed:12646332 ]
  4. Deshmukh SV, Nanovskaya TN, Hankins GD, Ahmed MS: N-demethylation of levo-alpha-acetylmethadol by human placental aromatase. Biochem Pharmacol. 2004 Mar 1;67(5):885-92. [PubMed:15104241 ]
  5. Nanovskaya TN, Deshmukh SV, Miles R, Burmaster S, Ahmed MS: Transfer of L-alpha-acetylmethadol (LAAM) and L-alpha-acetyl-N-normethadol (norLAAM) by the perfused human placental lobule. J Pharmacol Exp Ther. 2003 Jul;306(1):205-12. Epub 2003 Apr 3. [PubMed:12676878 ]
  6. Law F: Review: levomethadyl acetate hydrochloride improves retention in treatment and reduces heroin use in heroin dependence. Evid Based Ment Health. 2002 Nov;5(4):107. [PubMed:12440445 ]
  7. McCance-Katz EF, Rainey PM, Smith P, Morse G, Friedland G, Gourevitch M, Jatlow P: Drug interactions between opioids and antiretroviral medications: interaction between methadone, LAAM, and nelfinavir. Am J Addict. 2004 Mar-Apr;13(2):163-80. [PubMed:15204667 ]
  8. Skoulis NP, James RC, Harbison RD, Roberts SM: Depression of hepatic glutathione by opioid analgesic drugs in mice. Toxicol Appl Pharmacol. 1989 Jun 1;99(1):139-47. [PubMed:2471291 ]
  9. Cone EJ, Preston KL: Toxicologic aspects of heroin substitution treatment. Ther Drug Monit. 2002 Apr;24(2):193-8. [PubMed:11897965 ]
  10. Neff JA, Moody DE: Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4. Biochem Biophys Res Commun. 2001 Jun 15;284(3):751-6. [PubMed:11396966 ]
  11. Thomas BF, Jeffcoat AR, Myers MW, Mathews JM, Cook CE: Determination of l-alpha-acetylmethadol, l-alpha-noracetylmethadol and l-alpha-dinoracetylmethadol in plasma by gas chromatography-mass spectrometry. J Chromatogr B Biomed Appl. 1994 May 13;655(2):201-11. [PubMed:8081466 ]
  12. Grevert P, Masover B, Goldstein A: Failure of methadone and levomethadyl acetate (levo-alpha-acetylmethadol, LAAM) maintenance to affect memory. Arch Gen Psychiatry. 1977 Jul;34(7):849-53. [PubMed:879977 ]
  13. Vocci F, Ling W: Medications development: successes and challenges. Pharmacol Ther. 2005 Oct;108(1):94-108. [PubMed:16083966 ]
  14. Moody DE, Crouch DJ, Sakashita CO, Alburges ME, Minear K, Schulthies JE, Foltz RL: A gas chromatographic-positive ion chemical ionization-mass spectrometric method for the determination of I-alpha-acetylmethadol (LAAM), norLAAM, and dinorLAAM in plasma, urine, and tissue. J Anal Toxicol. 1995 Oct;19(6):343-51. [PubMed:8926727 ]
  15. Judson BA, Himmelberger DU, Goldstein A: The naloxone test for opiate dependence. Clin Pharmacol Ther. 1980 Apr;27(4):492-501. [PubMed:7357808 ]
  16. Eap CB, Bouchoux G, Scherbaum N, Gastpar M, Powell Golay K, Baumann P: Determination of human plasma levels of levo-alpha-acetylmethadol and its metabolites by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jun 5;805(1):141-6. [PubMed:15113550 ]
  17. Nelson AC, Huang W, Moody DE: Variables in human liver microsome preparation: impact on the kinetics of l-alpha-acetylmethadol (LAAM) n-demethylation and dextromethorphan O-demethylation. Drug Metab Dispos. 2001 Mar;29(3):319-25. [PubMed:11181502 ]
  18. Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML, Johnson RE: Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial. JAMA. 1997 Jun 25;277(24):1945-51. [PubMed:9200635 ]
  19. Cheever ML, Armendariz GA, Moody DE: Detection of methadone, LAAM, and their metabolites by methadone immunoassays. J Anal Toxicol. 1999 Oct;23(6):500-5. [PubMed:10517557 ]
  20. York RG, Denny KH, Moody DE, Alburges ME: Developmental toxicity of levo-alpha-acetylmethadol (LAAM) in tolerant rats. Int J Toxicol. 2002 Mar-Apr;21(2):147-59. [PubMed:12022632 ]
  21. Moody DE, Alburges ME, Parker RJ, Collins JM, Strong JM: The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. Drug Metab Dispos. 1997 Dec;25(12):1347-53. [PubMed:9394023 ]
  22. Krantz MJ, Mehler PS: Treating opioid dependence. Growing implications for primary care. Arch Intern Med. 2004 Feb 9;164(3):277-88. [PubMed:14769623 ]
  23. Deamer RL, Wilson DR, Clark DS, Prichard JG: Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM). J Addict Dis. 2001;20(4):7-14. [PubMed:11760927 ]
  24. Borzelleca JF, Egle JL Jr, Harris LS, Belleville JA: Toxicological evaluation of mu-agonists. Part II: Assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo-alpha-noracetylmethadol HCl (NorLAAM). J Appl Toxicol. 1995 Sep-Oct;15(5):339-55. [PubMed:8666717 ]
  25. Huang W, Bemis PA, Slawson MH, Moody DE: Determination of l-alpha-acetylmethadol (LAAM), norLAAM, and dinorLAAM in clinical and in vitro samples using liquid chromatography with electrospray ionization and tandem mass spectrometry. J Pharm Sci. 2003 Jan;92(1):10-20. [PubMed:12486677 ]
  26. Wilkins DG, Valdez AS, Krueger GG, Rollins DE: Quantitative analysis of l-alpha-acetylmethadol, l-alpha-acetyl-N-normethadol, and l-alpha-acetyl-N,N-dinormethadol in human hair by positive ion chemical ionization mass spectrometry. J Anal Toxicol. 1997 Oct;21(6):420-6. [PubMed:9323520 ]
  27. Jaffe JH, O'Keeffe C: From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States. Drug Alcohol Depend. 2003 May 21;70(2 Suppl):S3-11. [PubMed:12738346 ]
  28. Authors unspecified: Levomethadyl acetate to be used in narcotic treatment programs. Clin Pharm. 1993 Nov;12(11):797, 800. [PubMed:8275644 ]
  29. Jones HE, Strain EC, Bigelow GE, Walsh SL, Stitzer ML, Eissenberg T, Johnson RE: Induction with levomethadyl acetate: safety and efficacy. Arch Gen Psychiatry. 1998 Aug;55(8):729-36. [PubMed:9707384 ]
  30. Lott DC, Strain EC, Brooner RK, Bigelow GE, Johnson RE: HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate [corrected] buprenorphine, and methadone. J Subst Abuse Treat. 2006 Sep;31(2):187-94. Epub 2006 Jul 18. [PubMed:16919747 ]
  31. Vocci FJ, Acri J, Elkashef A: Medication development for addictive disorders: the state of the science. Am J Psychiatry. 2005 Aug;162(8):1432-40. [PubMed:16055764 ]
  32. McCance-Katz EF, Rainey PM, Smith P, Morse GD, Friedland G, Boyarsky B, Gourevitch M, Jatlow P: Drug interactions between opioids and antiretroviral medications: interaction between methadone, LAAM, and delavirdine. Am J Addict. 2006 Jan-Feb;15(1):23-34. [PubMed:16449090 ]
  33. Moody DE, Monti KM, Spanbauer AC: Long-term stability of abused drugs and antiabuse chemotherapeutical agents stored at -20 degrees C. J Anal Toxicol. 1999 Oct;23(6):535-40. [PubMed:10517563 ]
  34. Borg L, Ho A, Wells A, Joseph H, Appel P, Moody D, Kreek MJ: The use of levo-alpha-acetylmethadol (LAAM) in methadone patients who have not achieved heroin abstinence. J Addict Dis. 2002;21(3):13-22. [PubMed:12094997 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Oda Y, Kharasch ED: 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. J Pharmacol Exp Ther. 2001 Sep;298(3):1021-32. [PubMed:11504799 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular weight:
57882.48
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular weight:
44778.9
References
  1. Yu Y, Zhang L, Yin X, Sun H, Uhl GR, Wang JB: Mu opioid receptor phosphorylation, desensitization, and ligand efficacy. J Biol Chem. 1997 Nov 14;272(46):28869-74. [PubMed:9360954 ]
  2. Skoulis NP, James RC, Harbison RD, Roberts SM: Depression of hepatic glutathione by opioid analgesic drugs in mice. Toxicol Appl Pharmacol. 1989 Jun 1;99(1):139-47. [PubMed:2471291 ]
  3. Kreek MJ: Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci. 2000;909:186-216. [PubMed:10911931 ]
  4. Xiao Y, Smith RD, Caruso FS, Kellar KJ: Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs. J Pharmacol Exp Ther. 2001 Oct;299(1):366-71. [PubMed:11561100 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]