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			{{Short description|Synthetic opioid drug}}
	{{About|the synthetic opioid|the French singer|Laam|}}
			{{Redirect|LAAM||Laam (disambiguation)}}
	{{drugbox
			{{Drugbox
	| verifiedrevid = 407607788
			| Verifiedfields = changed
	| IUPAC_name = (1''S'',4''S'')-(6-dimethylamino-4,4-diphenyl-heptan-3-yl) acetate
			| Watchedfields = changed
	| image = Levacetylmethadol.svg
			| verifiedrevid = 411036921
	| width = 140
			| IUPAC_name = (3''S'',6''S'')-(6-dimethylamino-4,4-diphenyl-heptan-3-yl) acetate
	| CAS_number = 1477-40-3
			| image = Levacetylmethadol Formula V.1.svg
	| CAS_supplemental = <br />{{CAS|43033-72-3}} (])
	| ATC_prefix = N07		| width = 225px
			| image2 = LAAM-3D-vdW.png
	| ATC_suffix = BC03
	| PubChem = 15130		| width2 = 175px
	| DrugBank = APRD00745
			<!--Clinical data-->
	| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D04716		| tradename = OrLAAM
	| C = 23 | H = 31 | N = 1 | O = 2		| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
			| pregnancy_US = <!-- A / B / C / D / X -->
	| molecular_weight = 353.498
			| pregnancy_category = <!-- 3 -->
			| legal_AU = S8
			| legal_CA = Schedule I <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
			| legal_DE = Anlage III
			| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
			| legal_US = Schedule II
			| legal_status =
			| routes_of_administration = ]
			<!--Pharmacokinetic data-->
	| bioavailability =		| bioavailability =
	| protein_bound = ~80%		| protein_bound = ~80%
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	| elimination_half-life = 2.6 days		| elimination_half-life = 2.6 days
	| excretion =		| excretion =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
			<!--Identifiers-->
	| pregnancy_US = <!-- A / B / C / D / X -->
			| IUPHAR_ligand = 7212
	| pregnancy_category = <!-- 3 -->
			| CAS_number_Ref = {{cascite|correct|??}}
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
			| CAS_number = 1477-40-3
	| legal_CA = Schedule I <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
			| CAS_supplemental = <br />{{CAS|43033-72-3}} (])
	| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
			| ATC_prefix = N07
	| legal_US = Schedule II <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
	| legal_status =		| ATC_suffix = BC03
			| UNII_Ref = {{fdacite|changed|FDA}}
	| routes_of_administration = ]
			| UNII = R3B637Y991
			| KEGG_Ref = {{keggcite|correct|kegg}}
			| KEGG = D04716
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 1514
			| PubChem = 15130
			| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
			| DrugBank = DB01227
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 14401
			<!--Chemical data-->
			| C=23 | H=31 | N=1 | O=2
			| SMILES = CC(C(C(C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2)OC(=O)C
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 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
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = XBMIVRRWGCYBTQ-AVRDEDQJSA-N
	}}		}}
	'''Levacetylmethadol''' (]), '''levomethadyl acetate''' (]), '''Orlaam''' (trade name) or levo-α-acetylmethadol ('''LAAM''') is a synthetic ] similar in structure to ]. It has a long duration of action due to its active ]. It was approved in 1993 by the ] for use in the treatment of ]. In 2001, Orlaam was removed from the European market due to reports of life threatening ].<ref></ref> In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.<ref></ref>		'''Levacetylmethadol''' (]), '''levomethadyl acetate''' (]), '''OrLAAM''' (trade name) or levo-α-acetylmethadol ('''LAAM''')<ref>{{cite patent | country = US | number = 3021360 | title = 3-Acetoxy-4,4-diphenyl-6-methylaminoheptane | inventor = Pholand A | assign1 = Eli Lilly and Company | gdate = 12 February 1962 }}</ref><ref>{{cite patent | country = US | number = 2565592 | title = Alpha-d1-4-acetoxy-1-methyl-3,3-diphenylhexylamine and salts | inventor = Clark RL | assign1 = Merck & Company | gdate = 28 August 1951 }}</ref> is a synthetic ] similar in structure to ]. It has a long duration of action due to its active ].
	== Indications ==		==Medical uses==
	] is indicated as a second-line treatment for the treatment and management of ] if patients fail to respond to drugs like ] or ]. Before August, 1993 ] was classified as a ] drug in the United States. ] is not approved for use in ].		LAAM is indicated as a second-line treatment for the treatment and management of ] if patients fail to respond to drugs like ] or ].
			LAAM is used as an ] ] of LAAM ] at a concentration of 10&nbsp;mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with ] is 20–40&nbsp;mg. The first dose for patients who have been receiving ] will be a little higher than the amount of methadone that was being taken every day, but not more than 120&nbsp;mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered two to three times a week.
	== Chemistry and pharmacology ==
			==Pharmacology==
	Levacetylmethadyl acts as a ] ]. It also acts as a potent, ] ] neuronal ] ].<ref name="urlBlockade of Rat α3β4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs — JPET">{{cite web | url = http://jpet.aspetjournals.org/content/299/1/366.abstract | title = Blockade of Rat α3β4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs — JPET | work = | accessdate = }}</ref>
			===Pharmacodynamics===
	Levomethadyl acetate is the ''levo'' isomer of α-methadyl acetate. The ''dextro'' isomer is more potent but shorter acting. The ''levo'' isomer is also less toxic with an {{LD50}} in mice of 110&nbsp;mg/kg s.c. and 172.8&nbsp;mg/kg orally as opposed to {{LD50}}s of 61&nbsp;mg/kg s.c. and 118.3&nbsp;mg/kg orally for ''dl''-α-methadyl acetate. It has a ] of 215 °C and a ] of 353.50. β-methadyl acetate also exists, however it is more ] and less active than α-methadyl acetate and has no current medical use.
			LAAM acts as a ] ].<br />It also acts as a potent, ] ] neuronal ] ].<ref name="pmid11561100">{{cite journal | vauthors = Xiao Y, Smith RD, Caruso FS, Kellar KJ | title = Blockade of rat α3β4 nicotinic receptor function by methadone, its metabolites, and structural analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 299 | issue = 1 | pages = 366–71 | date = October 2001 | pmid = 11561100 | url = http://jpet.aspetjournals.org/content/299/1/366.short }}</ref>
			===Pharmacokinetics===
	Levomethadyl acetate undergoes extensive first-pass ] to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These ] are more potent than the parent drug.
			LAAM undergoes extensive ] to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These ] are more potent than the parent drug.
	== Dosing ==		==Chemistry==
			LAAM, or levomethadyl acetate, is the ''levo'' isomer of ], or α-methadyl acetate. The ''dextro'' isomer, ''d''-] (''d''-α-acetylmethadol), is more potent but shorter acting. The ''levo'' isomer is also less toxic with an {{LD50}} in mice of 110&nbsp;mg/kg s.c. and 172.8&nbsp;mg/kg orally as opposed to {{LD50}}s of 61&nbsp;mg/kg s.c. and 118.3&nbsp;mg/kg orally for ''dl''-α-methadyl acetate. It has a ] of 215&nbsp;°C and a ] of 353.50. β-methadyl acetate also exists, however it is more ] and less active than α-methadyl acetate and has no current medical use.
	LAAM is used as an ] ] of levomethadyl acetate ] at a concentration of 10&nbsp;mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with ] is 20–40&nbsp;mg. The first dose for patients who have been receiving ] will be a little higher than the amount of methadone that was being taken every day, but not more than 120&nbsp;mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered three times a week.
			==History==
			LAAM was approved in 1993 by the ] for use in the treatment of ]. In 2001, LAAM was removed from the European market due to reports of life-threatening ].<ref>{{cite web | work = The European Agency for the Evaluation of Medicinal Products | date = 19 April 2001 | url = http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/12/WC500018335.pdf | title = EMEA Public Statement on the Recommendation to Suspend the Marketing Authorisation for Orlaam (Levacetylmethadol) in the European Union | access-date = 4 April 2016 | archive-date = 4 February 2017 | archive-url = https://web.archive.org/web/20170204203042/http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/12/WC500018335.pdf | url-status = dead }}</ref> In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.<ref>{{cite web | url = https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153332.htm | archive-url = https://web.archive.org/web/20131010140220/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153332.htm | archive-date = 10 October 2013 | work = US FDA Safety Alerts | title = Orlaam (levomethadyl acetate hydrochloride) | date = 20 August 2013 }}</ref>
			==Society and culture==
			===Legal status===
			Before August 1993, LAAM was classified as a ] drug in the United States. LAAM is not approved for use in ] and ]. At present, it is a Schedule II Narcotic controlled substance in the United States with a DEA ACSCN of 9648 and a national aggregate annual manufacturing quota of 4 grams as of 2013.
	==References==		==References==
			{{Reflist}}
	<references/>
			== Further reading ==
			{{refbegin}}
			* {{cite journal | vauthors = Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML, Johnson RE | title = Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. A randomized clinical trial | journal = JAMA | volume = 277 | issue = 24 | pages = 1945–51 | date = June 1997 | pmid = 9200635 | doi = 10.1001/jama.1997.03540480045037}}
			* {{cite journal | vauthors = Jones HE, Strain EC, Bigelow GE, Walsh SL, Stitzer ML, Eissenberg T, Johnson RE | title = Induction with levomethadyl acetate: safety and efficacy. | journal = Archives of General Psychiatry | date = August 1998 | volume = 55 | issue = 8 | pages = 729–36 | doi = 10.1001/archpsyc.55.8.729 | pmid = 9707384 | doi-access = free }}
			{{refend}}
	==External links==		==External links==
	*		* {{cite web | url = https://www.drugs.com/cons/levomethadyl.html | title = LAAM Drug Information | work = Drugs.com }}
	*		* {{cite web | url = http://www.rxlist.com/cgi/generic2/levomethadyl_wcp.htm | work = RxList | title = Monograph for Orlaam | archive-url = https://web.archive.org/web/20080719082707/http://www.rxlist.com/cgi/generic2/levomethadyl_wcp.htm | archive-date = 2008-07-19 }}
	*		* {{cite web | url = https://go.drugbank.com/drugs/DB01227 | work = DrugBank | title = Levomethadyl Acetate }}
	* http://cat.inist.fr/?aModele=afficheN&cpsidt=2706063
	* http://cat.inist.fr/?aModele=afficheN&cpsidt=2390242
			{{Dependence treatment}}
	{{Antiaddictives}}
			{{Nicotinic acetylcholine receptor modulators}}
	{{Cholinergics}}
			{{Opioid receptor modulators}}
	]
	]
	]
	]		]
	]		]
			]
			]
	]
			]
	]
			]
	]
			]