Levomethadone
Synthetic opioid
From Wikipedia, the free encyclopedia
Levomethadone, sold under the brand name L-Polamidon among others, 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 is also the main therapeutic component of methadone, which is a racemic mixture of levomethadone (R-methadone) and dextromethadone (S-methadone).[2][4]
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| Other names | Levomethadone; R-Methadone, l-Methadone; 6R-Methadone; (–)-Methadone; R-(–)-Methadone; D-(–)-Methadone |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | By mouth, IV, IM, SC, IT[1] |
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| Pharmacokinetic data | |
| Bioavailability | High[1] |
| Protein binding | 60–90%[1] |
| Elimination half-life | ~18 hours[1] |
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| ECHA InfoCard | 100.120.592 |
| Chemical and physical data | |
| Formula | C21H27NO |
| Molar mass | 309.453 g·mol−1 |
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| Melting point | 99.5 °C (211.1 °F) |
| Solubility in water | 48.48 mg/mL (20 °C) |
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Levomethadone is used for narcotic maintenance in place of, or in some cases alongside as an alternative, to racemic methadone,[5] owing to concern that the cardiotoxic and QT-prolonging action of racemic methadone might be primarily caused by dextromethadone.[6][5]
Pharmacology
Pharmacodynamics
Levomethadone has approximately 50x the potency of the S-(+)-enantiomer as well as greater μ-opioid receptor selectivity.[1][7] Accordingly, it is about twice as potent as methadone by weight and its effects are virtually identical in comparison.[8][9] 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[10] and as a potent noncompetitive antagonist of the α3β4 nicotinic acetylcholine (nACh) receptor.[11]
| Compound | Affinities (Ki, in nM) | Ratios | ||||||
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| MOR | DOR | KOR | SERT | NET | NMDAR | M:D:K | SERT:NET | |
| Racemic methadone | 1.7 | 435 | 405 | 1,400 | 259 | 2,500–8,300 | 1:256:238 | 1:5 |
| Dextromethadone | 19.7 | 960 | 1,370 | 992 | 12,700 | 2,600–7,400 | 1:49:70 | 1:13 |
| Levomethadone | 0.945 | 371 | 1,860 | 14.1 | 702 | 2,800–3,400 | 1:393:1968 | 1:50 |
Chemistry
The separation of the stereoisomers is one of the easier in organic chemistry and is described in the original patent.[14] 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."[15]
There is now an asymmetric synthesis[16] available to prepare both levomethadone (R-(−)-methadone) and dextromethadone (S-(+)-methadone).[17]
Society and culture
Generic names
Levomethadone is the generic name of the drug and its INN.[3][2]
Brand names
Levomethadone has been sold under brand names including L-Polaflux, L-Polamidon, L-Polamivet, Levadone, Levo-Methasan, Levothyl, Mevodict, Levopidon and Vistadict, among others.[18][3][2]
Legal 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.[19] It is similarly controlled under the German Betäubungsmittelgesetz and similar laws in practically every other country.[20][21]