The separation of the stereoisomers is one of the easier in organic chemistry and is described in the original patent.[13] It involves "treatment of racemic methadone base with d-(+)-tartaric acid in an acetone/water mixture [which] precipitates almost solely the dextro-methadone levo-tartrate, and the more potent Levomethadone can easily be retrieved from the mother liquor in a high state of optical purity."[14]
There is now an asymmetric synthesis[15] available to prepare both levomethadone (R-(−)-methadone) anddextromethadone (S-(+)-methadone).[16]
Levomethadone has been sold under brand names including L-Polaflux, L-Polamidon, L-Polamivet, Levadone, Levo-Methasan, Levothyl, Mevodict, Levopidon and Vistadict, among others.[17][3][2]
Levomethadone is listed under theSingle Convention On Narcotic Drugs 1961 and is a Schedule II Narcotic controlled substance in the US as an isomer of methadone (ACSCN 9250) and is not listed separately, nor is dextromethadone.[18] It is similarly controlled under the GermanBetäubungsmittelgesetz and similar laws in practically every other country.[19][20]
^abJudson BA, Horns WH, Goldstein A (October 1976). "Side effects of levomethadone and racemic methadone in a maintenance program".Clinical Pharmacology and Therapeutics.20 (4):445–449.doi:10.1002/cpt1976204445.PMID788990.
^Eap CB, Crettol S, Rougier JS, Schläpfer J, Sintra Grilo L, Déglon JJ, et al. (May 2007). "Stereoselective Block of hERG Channel by (S)-Methadone and QT Interval Prolongation in CYP2B6 Slow Metabolizers".Clinical Pharmacology and Therapeutics.81 (5):719–728.doi:10.1038/sj.clpt.6100120.PMID17329992.
^Verthein U, Ullmann R, Lachmann A, Düring A, Koch B, Meyer-Thompson HG, et al. (November 2005). "The effects of racemic D,L-methadone and L-methadone in substituted patients--a randomized controlled study".Drug and Alcohol Dependence.80 (2):267–271.doi:10.1016/j.drugalcdep.2005.04.007.PMID15916866.
^Xiao Y, Smith RD, Caruso FS, Kellar KJ (October 2001). "Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs".The Journal of Pharmacology and Experimental Therapeutics.299 (1):366–371.doi:10.1016/S0022-3565(24)29338-1.PMID11561100.
^Gorman AL, Elliott KJ, Inturrisi CE (February 1997). "The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord".Neurosci. Lett.223 (1):5–8.doi:10.1016/S0304-3940(97)13391-2.PMID9058409.
^Hull JD, Scheinmann F, Turner NJ (March 2003). "Synthesis of optically active methadones, LAAM and bufuralol by lipase-catalysed acylations".Tetrahedron: Asymmetry.14 (5):567–576.doi:10.1016/S0957-4166(03)00019-3.
^US 6143933, Scheinmann F, Hull JD, Turner NJ, "Process for the preparation of optically active methadones in high enantiomeric purity", issued 7 November 2000, assigned to Salford Ultrafine Chemicals.
