Levorphanol

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Levorphanol
Structural formula
Ball-and-stick model
Clinical data
Trade names Levo-Dromoran
Synonyms Ro 1-5431[1]
AHFS/Drugs.com Monograph
MedlinePlus a682020
Pregnancy
category
  • US: C (Risk not ruled out)
Dependence
liability
High
Routes of
administration
Oral, intravenous, subcutaneous, intramuscular
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability 70% (oral); 100% (IV)
Protein binding 40%
Metabolism Hepatic
Elimination half-life 11–16 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.000.912 Edit this at Wikidata
Chemical and physical data
Formula C17H23NO
Molar mass 257.371 g/mol
3D model (JSmol)
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Levorphanol (INN; brand name Levo-Dromoran) is an opioid medication used to treat moderate to severe pain.[1][2][3] It is one of four enantiomers of the compound racemorphan, and was first described in Germany in 1948 as an orally active, morphine-like analgesic.[4] The drug has been in clinical use in the United States since 1953.[5]

Pharmacology[edit]

Levorphanol acts predominantly as an agonist of the μ-opioid receptor (MOR), but is also an agonist of the δ-opioid receptor (DOR), κ-opioid receptor (KOR), and the nociceptin receptor (NOP), as well as an NMDA receptor antagonist and a serotonin-norepinephrine reuptake inhibitor (SNRI).[5] Levorphanol, similarly to certain other opioids, also acts as a glycine receptor antagonist and GABA receptor antagonist at very high concentrations.[6] Levorphanol is 6 to 8 times as potent as morphine at the MOR.[citation needed]

Relative to morphine, levorphanol lacks complete cross-tolerance[7] and possesses greater intrinsic activity at the MOR.[7] The duration 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 the phenylheptylamine open-chain opioids such as methadone or the phenylpiperidine ketobemidone, make levorphanol useful for types of pain that other analgesics may not be as effective against, such as neuropathic pain.[8] Levorphanol's exceptionally high analgesic efficacy in the treatment of neuropathic pain is also conferred by its action on serotonin and norepinephrine transporters, similar to the opioids tramadol and tapentadol, and mutually complements the analgesic effect of its NMDA receptor antagonism.[9]

Levorphanol shows a high rate of psychotomimetic side effects such as hallucinations and delirium, which have been attributed to its binding to and activation of the KOR.[10] At the same time however, activation of this receptor as well as of the DOR have been determined to contribute to its analgesic effects.[10]

Chemistry[edit]

Levorphanol and its stereoisomer dextrorphan, the enantiomers of the racemic mixture racemorphan.

Chemically, levorphanol belongs to the morphinan class and is (−)-3-hydroxy-N-methyl-morphinan.[7] It is the "left-handed" (levorotatory) stereoisomer of racemorphan, that is the racemic mixture of the two stereoisomers with differing pharmacology. The "right-handed" (dextrorotatory) enantiomer of racemorphan is dextrorphan (DXO), an antitussive, potent dissociative hallucinogen (NMDA receptor antagonist), and weakly active opioid. DXO is an active metabolite of the pharmaceutical drug dextromethorphan (DXM), which, analogously to DXO, is an enantiomer of the racemic mixture racemethorphan along with levomethorphan, the latter of which has similar properties to those of levorphanol.

Society and culture[edit]

Name[edit]

Levorphanol is the INN, BAN, and DCF.[1][2][3] As the medically used tartrate salt, the drug is also known as levorphanol tartrate (USAN, BANM).[1][3] The former developmental code name of levorphanol at Roche was Ro 1-5431.[1][3]

Availability[edit]

As the tartrate salt, levorphanol is marketed by Roche in the U.S. and Canada under the brand name Levo-Dromoran.[2]

Legality[edit]

Levorphanol is listed under the Single Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the U.S., it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9220 and 2013 annual aggregate manufacturing quota of 4.5 kilos. The salts in use are the tartrate (free base conversion ratio 0.58) and hydrobromide (0.76).[11]

References[edit]

  1. ^ a b c d e J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 656–. ISBN 978-1-4757-2085-3. 
  2. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 606–. ISBN 978-3-88763-075-1. 
  3. ^ a b c d I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 165–. ISBN 978-94-011-4439-1. 
  4. ^ DE 1014545 
  5. ^ a b Gudin, Jeffrey; Fudin, Jeffrey; Nalamachu, Srinivas (2015). "Levorphanol Use: Past, Present and Future". Postgraduate Medicine. 128: 46–53. doi:10.1080/00325481.2016.1128308. ISSN 0032-5481. 
  6. ^ Neville N. Osborne (22 October 2013). Selected Topics from Neurochemistry. Elsevier Science. pp. 244–. ISBN 978-1-4832-8635-8. 
  7. ^ a b c Davis, MP; Glare, PA; Hardy, J (2009) [2005]. Opioids in Cancer Pain (2nd ed.). Oxford, UK: Oxford University Press. ISBN 978-0-19-157532-7. 
  8. ^ Prommer, E (2007). "Levorphanol: the forgotten opioid". Supportive Care in Cancer. 15 (3): 259–264. doi:10.1007/s00520-006-0146-2. PMID 17039381. 
  9. ^ Nalamachu, S; Gudin, J (Apr 2016). "Levorphanol, another choice in opioid rotation". J Pain. 17: S14. doi:10.1016/j.jpain.2016.01.056. PMID 28162375. 
  10. ^ a b Eduardo D. Bruera; Russell K. Portenoy (12 October 2009). Cancer Pain: Assessment and Management. Cambridge University Press. pp. 215–. ISBN 978-0-521-87927-9. 
  11. ^ deadiversion.usdoj.gov