Levorphanol

Levorphanol
Structural formula
Ball-and-stick model
Clinical data
Trade names Levo-dromoran
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
Biological half-life 11-16 hours
Identifiers
CAS Number 77-07-6 YesY
PubChem (CID) 5359272
IUPHAR/BPS 7595
DrugBank DB00854 YesY
ChemSpider 16736212 YesY
UNII 27618J1N2X YesY
KEGG D08123 YesY
ChEMBL CHEMBL592 N
ECHA InfoCard 100.000.912
Chemical and physical data
Formula C17H23NO
Molar mass 257.371 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Levorphanol /lɛvaʊrfɑːnɒl/ (brand name Levo-Dromoran) is an opioid medication used to treat moderate to severe pain. Chemically, it is (−)-3-hydroxy-N-methyl-morphinan.[1] It is the levorotatory stereoisomer of racemorphan, first described in Germany in 1948 as an orally-active morphine-like analgesic.[2] It has been in clinical use in the U.S. since 1953.[3]

Levorphanol acts predominantly as an agonist of the μ-opioid receptor, but is also an agonist of the δ-opioid, κ-opioid, and nociceptin receptors, as well as an NMDA receptor antagonist and a serotonin-norepinephrine reuptake inhibitor.[3] Levorphanol, similarly to certain other opioids, also acts as a glycine receptor antagonist and GABA receptor antagonist at very high concentrations.[4] Levorphanol is 6-8 times as potent as morphine at the mu-opioid receptor.

Relative to morphine, levorphanol lacks complete cross-tolerance [1] and possesses greater intrinsic activity at the MOR.[1] 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 favourable of the strong narcotics. Its NMDA actions, similar to those of the phenylheptylamine open-chain narcotics 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.[5] Levorphanol's exceptionally high analgesic efficacy in the treatment of neuropathy 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 antagonization.

Levorphanol shows a high rate of psychotomimetic effects such as hallucinations and delirium, which have been attributed to by its binding to and activation of the κ-opioid receptor.[6] However, activation of this receptor as well as of the δ-opioid receptor have been determined to contribute to its analgesic effects.[6]

Levorphanol is listed under the Single Convention On Narcotic Drugs 1961 and is regulated like morphine in most countries. In the United States 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).[7]

See also

References

  1. 1 2 3 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.
  2. ↑ DE 1014545
  3. 1 2 Gudin, Jeffrey; Fudin, Jeffrey; Nalamachu, Srinivas (2015). "Levorphanol Use: Past, Present and Future". Postgraduate Medicine. doi:10.1080/00325481.2016.1128308. ISSN 0032-5481.
  4. ↑ Neville N. Osborne (22 October 2013). Selected Topics from Neurochemistry. Elsevier Science. pp. 244–. ISBN 978-1-4832-8635-8.
  5. ↑ Prommer, E (2007). "Levorphanol: the forgotten opioid.". Supportive Care in Cancer. 15 (3): 259–264. doi:10.1007/s00520-006-0146-2. PMID 17039381.
  6. 1 2 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.
  7. ↑ http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html


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