Levorphanol: the forgotten opioid
Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a strong opioid that is the only available opioid agonist of the morphinan series. Levorphanol was originally synthesized as a pharmacological alternative to morphine more than 40 years ago. It is considered a step-3 opioid by the World Health Organization (WHO) and has a greater potency than morphine. Analgesia produced by levorphanol is mediated via its interactions with μ, δ, and κ opioid receptors. Levorphanol is also an N-methyl-d-aspartate (NMDA) receptor antagonist. There is evidence that levorphanol may inhibit uptake of norepinephrine and serotonin. Similar to morphine, levorphanol undergoes glucuronidation in the liver, and the glucuronidated products are excreted in the kidney. Levorphanol can be given orally, intravenously, and subcutaneously.
This article reviews the pharmacodynamics, pharmacology, and clinical efficacy for this often overlooked step-3 opioid.
The long half-life of the drug increases the potential for drug accumulation. Levorphanol has clinical efficacy in neuropathic pain.
KeywordsPain Levorphanol Opioids NMDA Glucuronidation
- 2.Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, Mercadante S, Meynadier J, Poulain P, Ripamonti C, Radbruch L, Casas JR, Sawe J, Twycross RG, Ventafridda V; Expert Working Group of the Research Network of the European Association for Palliative Care (2001) Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 84(5):587–593PubMedCrossRefGoogle Scholar
- 4.Payne R, Gonzalez GR (2004) The management of pain. In: Geoffrey DD, Hanks WC, MacDonald N (eds) Oxford textbook of palliative medicine. Oxford Medical PublicationsGoogle Scholar
- 6.Zhang A, Xiong W, Bidlack JM, Hilbert JE, Knapp BI, Wentland MP, Neumeyer JL (2004) 10-Ketomorphinan and 3-substituted-3-desoxymorphinan analogues as mixed kappa and micro opioid ligands: synthesis and biological evaluation of their binding affinity at opioid receptors. J Med Chem 47(1):165–174PubMedCrossRefGoogle Scholar
- 7.Wang Y, Li JG, Huang P, Xu W, Liu-Chen LY (2003) Differential effects of agonists on adenylyl cyclase superactivation mediated by the kappa opioid receptors: adenylyl cyclase superactivation is independent of agonist-induced phosphorylation, desensitization, internalization, and down-regulation. J Pharmacol Exp Ther 307(3):1127–1134PubMedCrossRefGoogle Scholar
- 11.Stringer M, Makin MK, Miles J, Morley JS (2000) d-morphine, but not l-morphine, has low micromolar affinity for the non-competitive N-methyl-d-aspartate site in rat forebrain. Possible clinical implications for the management of neuropathic pain. Neurosci Lett 295(1–2):21–24PubMedCrossRefGoogle Scholar
- 14.Product Information: levorphanol tartrate tablets USP. 2004Google Scholar
- 15.Micromedex healthcare series. 2005Google Scholar