| Record Information |
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| Version | 2.0 |
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| Creation Date | 2009-07-21 20:28:41 UTC |
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| Update Date | 2014-12-24 20:25:56 UTC |
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| Accession Number | T3D3027 |
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| Identification |
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| Common Name | Levomethadyl Acetate |
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| Class | Small Molecule |
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| Description | Levomethadyl 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. |
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| Compound Type | - Amine
- Analgesic, Opioid
- Drug
- Ester
- Ether
- Metabolite
- Narcotic
- Organic Compound
- Synthetic Compound
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| Chemical Structure | |
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| Synonyms | | Synonym | | (-)-alpha-Acetylmethadol | | (1S,4S)-4-(dimethylamino)-1-Ethyl-2,2-diphenylpentyl acetate | | 1-alpha-Acetylmethadol | | LAAM | | Levacetilmetadol | | Levacetylmethadol | | Levacetylmethadolum | | Levo-alpha-acetylmethadol | | Levo-Alphacetylmethadol | | Levo-Methadyl Acetate | | Levo-α-acetylmethadol | | Levomethadyl | | Levomethadyl acetate | | Levomethadyl acetic acid | | Nor-LAAM | | Orlaam |
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| Chemical Formula | C23H31NO2 |
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| Average Molecular Mass | 353.498 g/mol |
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| Monoisotopic Mass | 353.235 g/mol |
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| CAS Registry Number | 1477-40-3 |
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| IUPAC Name | (3S,6S)-6-(dimethylamino)-4,4-diphenylheptan-3-yl acetate |
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| Traditional Name | levomethadyl acetate |
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| SMILES | [H][C@](C)(CC(C1=CC=CC=C1)(C1=CC=CC=C1)[C@]([H])(CC)OC(C)=O)N(C)C |
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| 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 |
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| InChI Key | InChIKey=XBMIVRRWGCYBTQ-AVRDEDQJSA-N |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Benzenoids |
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| Class | Benzene and substituted derivatives |
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| Sub Class | Diphenylmethanes |
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| Direct Parent | Diphenylmethanes |
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| Alternative Parents | |
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| 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
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| Molecular Framework | Aromatic homomonocyclic compounds |
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| External Descriptors | |
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| Biological Properties |
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| Status | Detected and Not Quantified |
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| Origin | Exogenous |
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| Cellular Locations | |
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| Biofluid Locations | Not Available |
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| Tissue Locations | Not Available |
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| Pathways | Not Available |
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| Applications | |
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| Biological Roles | |
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| Chemical Roles | Not Available |
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| Physical Properties |
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| State | Solid |
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| Appearance | White powder. |
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| Experimental Properties | | Property | Value |
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| Melting Point | v . d . e Drugs used in addictive disorders ( N07B ) | | Boiling Point | Not Available | | Solubility | >15 mg/mL | | LogP | 5.4 |
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| Predicted Properties | |
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| Spectra |
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| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
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| Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0uk9-9081000000-c21fec0e8e70744482b4 | 2017-09-01 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0udi-0029000000-c28a76d17f554d7ba439 | 2016-06-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-022c-7096000000-e5337d3be9cfb3f23f09 | 2016-06-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0fkc-5190000000-113274c2b46b6767d5b3 | 2016-06-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0udi-1019000000-248c95ec24dae3299384 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0nmi-4039000000-abf719229500214241e6 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-05mo-9081000000-e357c686965cbd06e26c | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0udi-0089000000-c427737dde1e774f4972 | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0pb9-2193000000-2a568014680a63d6012f | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-06di-3790000000-c1eca86692e210363e6a | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-0zfr-6019000000-270678fc70b14132747a | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-0a4i-9000000000-c01bbbf5bed889264ddb | 2021-10-11 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-056r-2930000000-da1f57c344e66e9ff112 | 2021-10-11 | View Spectrum |
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| Toxicity Profile |
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| Route of Exposure | Levomethadyl acetate is rapidly absorbed from an oral solution. |
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| Mechanism of Toxicity | 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. |
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| Metabolism | Levomethadyl 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 |
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| Toxicity Values | Not Available |
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| Lethal Dose | Not Available |
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| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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| Uses/Sources | For the treatment and management of opiate dependence. It is sometimes used to treat severe pain in terminal patients. |
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| Minimum Risk Level | Not Available |
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| Health Effects | Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. |
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| Symptoms | Signs of overdose include apnea, circulatory collapse, pulmonary edema, cardiac arrest, and death. |
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| Treatment | In 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) |
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| Normal Concentrations |
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| Not Available |
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| Abnormal Concentrations |
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| Not Available |
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| External Links |
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| DrugBank ID | DB01227 |
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| HMDB ID | HMDB15358 |
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| PubChem Compound ID | 15130 |
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| ChEMBL ID | CHEMBL1514 |
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| ChemSpider ID | 14401 |
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| KEGG ID | C08012 |
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| UniProt ID | Not Available |
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| OMIM ID | |
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| ChEBI ID | 6441 |
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| BioCyc ID | Not Available |
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| CTD ID | Not Available |
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| Stitch ID | Levomethadyl Acetate |
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| PDB ID | Not Available |
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| ACToR ID | Not Available |
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| Wikipedia Link | Levomethadyl_Acetate |
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| References |
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| Synthesis Reference | Not Available |
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| MSDS | Not Available |
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| General References | - 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. [11058673 ]
- 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. [12220607 ]
- 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. [12646332 ]
- 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. [15104241 ]
- 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. [12676878 ]
- 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. [12440445 ]
- 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. [15204667 ]
- 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. [2471291 ]
- Cone EJ, Preston KL: Toxicologic aspects of heroin substitution treatment. Ther Drug Monit. 2002 Apr;24(2):193-8. [11897965 ]
- 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. [11396966 ]
- 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. [8081466 ]
- 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. [879977 ]
- Vocci F, Ling W: Medications development: successes and challenges. Pharmacol Ther. 2005 Oct;108(1):94-108. [16083966 ]
- 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. [8926727 ]
- Judson BA, Himmelberger DU, Goldstein A: The naloxone test for opiate dependence. Clin Pharmacol Ther. 1980 Apr;27(4):492-501. [7357808 ]
- 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. [15113550 ]
- 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. [11181502 ]
- 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. [9200635 ]
- 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. [10517557 ]
- 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. [12022632 ]
- 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. [9394023 ]
- Krantz MJ, Mehler PS: Treating opioid dependence. Growing implications for primary care. Arch Intern Med. 2004 Feb 9;164(3):277-88. [14769623 ]
- 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. [11760927 ]
- 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. [8666717 ]
- 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. [12486677 ]
- 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. [9323520 ]
- 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. [12738346 ]
- Levomethadyl acetate to be used in narcotic treatment programs. Clin Pharm. 1993 Nov;12(11):797, 800. [8275644 ]
- 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. [9707384 ]
- 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. [16919747 ]
- 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. [16055764 ]
- 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. [16449090 ]
- 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. [10517563 ]
- 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. [12094997 ]
- Drugs.com [Link]
- RxList: The Internet Drug Index (2009). [Link]
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| Gene Regulation |
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| Up-Regulated Genes | Not Available |
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| Down-Regulated Genes | Not Available |
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