Levomethadone

Levomethadone

Levomethadone
Systematic (IUPAC) name
(6R)-6-(dimethylamino)-4,4-diphenyl-3-heptanone
Clinical data
AHFS/Drugs.com
Legal status
Routes Oral, IV, IM, SC, IT[1]
Pharmacokinetic data
Bioavailability High[1]
Protein binding 60-90%[1]
Half-life ~18 hours[1]
Identifiers
CAS number
5967-73-7 (HCl)
ATC code N07
PubChem
ChemSpider
Chemical data
Formula C21H27NO 
Mol. mass 309.445 g/mol

Levomethadone (INN; L-Polamidon, L-Polamivet, Levadone, Levothyl), or levamethadone, is a synthetic opioid analgesic and antitussive which is marketed in Europe and is used for pain management and in opioid maintenance therapy.[1][2][3] In addition to being used as a pharmaceutical drug itself, levomethadone, or R-(-)-methadone, is the active enantiomer of methadone,[2] having approximately 50x the potency of the S-(+)-enantiomer as well as greater μ-opioid receptor selectivity.[1][4] Accordingly, it is about twice as potent as methadone by weight and its effects are virtually identical in comparison.[5][6] In addition to its activity at the opioid receptors, levomethadone has been found to act as a weak competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor complex[7] and as a potent noncompetitive antagonist of the α3β4 nicotinic acetylcholine (nACh) receptor.[8]

There is now an asymmetric synthesis[9] available to prepare both levomethadone [R-(-)-methadone] and dextromethadone [S-(+)-methadone].[10]

The separation of the stereoisomers is one of the easier in organic chemistry and is described in the original patent. 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 levo-methadone can easily be retrieved from the mother liquor in a high state of optical purity" [11]

Regulatory status

Levomethadone is listed under the Single 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.[12] It is similarly controlled under the German Betäubungsmittelgesetz and similar laws in practically every other country.

See also

References

  1. ^ a b c d e f Helmut Buschmann (20 December 2002). Analgesics: From Chemistry and Pharmacology to Clinical Application. Wiley-VCH. p. 196.  
  2. ^ a b F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1294.  
  3. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 605.  
  4. ^ Renate Förch; Holger Schönherr; A. Tobias A. Jenkins (11 August 2009). Surface Design: Applications in Bioscience and Nanotechnology. Wiley-VCH. p. 193.  
  5. ^ Eduardo Bruera; Sriram Yennurajalingam (16 August 2011). Oxford American Handbook of Hospice and Palliative Medicine. Oxford University Press. p. 43.  
  6. ^ Verthein U, Ullmann R, Lachmann A, 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): 267–71.  
  7. ^ Eric C. Strain; Maxine L. Stitzer (4 November 2005). The Treatment of Opioid Dependence. JHU Press. p. 63.  
  8. ^ 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): 366–71.  
  9. ^ 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.  
  10. ^ US patent 6143933 
  11. ^ https://www.erowid.org/archive/rhodium/chemistry/methadone.html
  12. ^ http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html