Levomethadyl Acetate (CHEM002381)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (3)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:41 UTC
Update Date2016-11-09 01:08:45 UTC
Accession NumberCHEM002381
Identification
Common NameLevomethadyl Acetate
ClassSmall Molecule
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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
Contaminant Type
  • Amine
  • Analgesic, Opioid
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Narcotic
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
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 Mass353.498 g/mol
Monoisotopic Mass353.235 g/mol
CAS Registry Number1477-40-3
IUPAC Name(3S,6S)-6-(dimethylamino)-4,4-diphenylheptan-3-yl acetate
Traditional Namelevomethadyl acetate
SMILESCC[C@H](OC(C)=O)C(C[C@H](C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1
InChI IdentifierInChI=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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Pointv . d . e Drugs used in addictive disorders ( N07B )
Boiling PointNot Available
Solubility>15 mg/mL
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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0uk9-9081000000-c21fec0e8e70744482b4Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
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
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0089000000-c427737dde1e774f4972Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0pb9-2193000000-2a568014680a63d6012fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06di-3790000000-c1eca86692e210363e6aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0zfr-6019000000-270678fc70b14132747aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-c01bbbf5bed889264ddbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-2930000000-da1f57c344e66e9ff112Spectrum
Toxicity Profile
Route of ExposureLevomethadyl acetate is rapidly absorbed from an oral solution.
Mechanism of ToxicityOpiate 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.
MetabolismLevomethadyl acetate undergoes extensive first-pass metabolism to the active demethylated metabolite nor-levomethadyl acetate, which is further demethylated to a second active metabolite, dinor-levomethadyl acetate. These metabolites are more potent than the parent drug. Half Life: 2.6 days
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment and management of opiate dependence. It is sometimes used to treat severe pain in terminal patients.
Minimum Risk LevelNot Available
Health EffectsMedical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.
SymptomsSigns of overdose include apnea, circulatory collapse, pulmonary edema, cardiac arrest, and death.
TreatmentIn the case of Levomethadyl Acetate overdose, protect the patient's airway and support ventilation and circulation. Absorption of Levomethadyl Acetate from the gastrointestinal tract may be decreased by gastric emptying and/or administration of activated charcoal. (Safeguard the patient's airway when employing gastric emptying or administering charcoal in any patient with diminished consciousness). Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion are unlikely to be beneficial for Levomethadyl Acetate overdose due to its high lipid solubility and large volume of distribution. Naloxone may be given to antagonize opiate effects, but the airway must be secured as vomiting may ensue. If possible, naloxone should be titrated to clinical effect rather than given as a large single bolus, since rapid reversal of opioid effects by large naloxone doses can cause severe precipitated withdrawal effects that may include cardiac instability. If a patient has received a total of 10 mg of naloxone without clinical response, the diagnosis of opioid overdose is unlikely. If the patient does respond to naloxone, the physician should remember that the duration of Levomethadyl Acetate activity is much longer (days) than that of naloxone (minutes) and repeated dosing with or continuous intravenous infusion of naloxone is likely to be required. Use of oral naltrexone in this setting is not recommended because it may precipitate prolonged opioid withdrawal symptoms. (36)
Concentrations
Not Available
DrugBank IDDB01227
HMDB IDHMDB0015358
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkLevomethadyl_Acetate
Chemspider ID14401
ChEBI ID6441
PubChem Compound ID15130
Kegg Compound IDC08012
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot 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.
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.
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.
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.
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.
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.
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.
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.
9. Cone EJ, Preston KL: Toxicologic aspects of heroin substitution treatment. Ther Drug Monit. 2002 Apr;24(2):193-8.
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.
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.
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.
13. Vocci F, Ling W: Medications development: successes and challenges. Pharmacol Ther. 2005 Oct;108(1):94-108.
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.
15. Judson BA, Himmelberger DU, Goldstein A: The naloxone test for opiate dependence. Clin Pharmacol Ther. 1980 Apr;27(4):492-501.
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.
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.
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.
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.
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.
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.
22. Krantz MJ, Mehler PS: Treating opioid dependence. Growing implications for primary care. Arch Intern Med. 2004 Feb 9;164(3):277-88.
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.
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.
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.
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.
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.
28. Authors unspecified: Levomethadyl acetate to be used in narcotic treatment programs. Clin Pharm. 1993 Nov;12(11):797, 800.
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.
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.
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.
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.
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.
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.