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| Clinical data | |
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| Trade names | Levo-Dromoran |
| Other names | Ro 1-5431[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682020 |
| Routes of administration | Oral, intravenous, subcutaneous, intramuscular |
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| Pharmacokinetic data | |
| Bioavailability | 70% (oral); 100% (IV) |
| Protein binding | 40% |
| Metabolism | Hepatic |
| Eliminationhalf-life | 11–16 hours |
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| ECHA InfoCard | 100.000.912 |
| Chemical and physical data | |
| Formula | C17H23NO |
| Molar mass | 257.377 g·mol−1 |
| 3D model (JSmol) | |
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Levorphanol (brand nameLevo-Dromoran) is anopioid medication used to treat moderate to severepain.[1][3][4] It is thelevorotatoryenantiomer of the compoundracemorphan. Itsdextrorotatory counterpart isdextrorphan.
It was first described inGermany in 1946.[5] The drug has been in medical use in theUnited States since 1953.[6]
Levorphanol acts predominantly as anagonist of theμ-opioid receptor (MOR), but is also an agonist of theδ-opioid receptor (DOR),κ-opioid receptor (KOR), and thenociceptin receptor (NOP), as well as anNMDA receptor antagonist and aserotonin-norepinephrine reuptake inhibitor (SNRI).[6] Levorphanol, similarly to certain other opioids, also acts as aglycine receptor antagonist andGABA receptor antagonist at very high concentrations.[7] As per the World Health Organization, levorphanol is a step 3 opioid and is considered eight times more potent than morphine at the MOR (2 mg levorphanol is equivalent to 15 mg morphine).[citation needed]
Relative to morphine, levorphanol lacks completecross-tolerance[8] and possesses greaterintrinsic activity at the MOR.[8] Theduration of action is generally long compared to other comparable analgesics and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favorable of the strong narcotics. Its antagonism of the NMDA receptor, similar to those of thephenylheptylamine open-chain opioids such asmethadone or thephenylpiperidineketobemidone, make levorphanol useful for types of pain that other analgesics may not be as effective against, such asneuropathic pain.[9] Levorphanol's exceptionally high analgesic efficacy in the treatment of neuropathic pain is also conferred by its action onserotonin andnorepinephrine transporters, similar to the opioidstramadol andtapentadol, and mutually complements the analgesic effect of its NMDA receptor antagonism.[10]
Levorphanol shows a high rate ofpsychotomimeticside effects such ashallucinations anddelirium, which have been attributed to its binding to and activation of the KOR.[11] At the same time however, activation of this receptor as well as of the DOR have been determined to contribute to its analgesic effects.[11]
Chemically, levorphanol belongs to themorphinan class and is (−)-3-hydroxy-N-methyl-morphinan.[8] It is the "left-handed" (levorotatory)stereoisomer ofracemorphan, theracemic mixture of the two stereoisomers with differingpharmacology. The "right-handed" (dextrorotatory) enantiomer of racemorphan isdextrorphan (DXO), anantitussive, potentdissociativehallucinogen (NMDA receptor antagonist), and weakly active opioid. DXO is anactive metabolite of thepharmaceutical drugdextromethorphan (DXM), which, analogously to DXO, is an enantiomer of the racemic mixtureracemethorphan along withlevomethorphan, the latter of which has similar properties to those of levorphanol.
Levorphanol is theINN,BAN, andDCF.[1][3][4] As the medically usedtartratesalt, the drug is also known aslevorphanol tartrate (USAN,BANM).[1][4] The former developmental code name of levorphanol atRoche wasRo 1-5431.[1][4]
As the tartrate salt, levorphanol is marketed by Hikma Pharmaceuticals USA Inc.[12] and Virtus Pharmaceuticals in the U.S., andCanada under the brand nameLevo-Dromoran.[3]
Levorphanol is listed under theSingle Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the U.S., it is aSchedule II Narcoticcontrolled substance with aDEAACSCN of 9220 and 2013 annual aggregate manufacturing quota of 4.5 kilograms. The salts in use are the tartrate (free base conversion ratio 0.58) andhydrobromide (0.76).[13]