Now Testing - Levorphanol/Dextrorphan

PremierTox® Laboratory will be updating the description of test 139 – Levorphanol Confirmation and its final results reporting, to now include its stereoisomer - dextrorphan.  Effective June 8, confirmation testing for levorphanol/dextrorphan may be ordered as 139 – Levorphanol / Dextrorphan.

There are several classifications of stereoisomers.  Levorphanol and dextrophan are two compounds that are structurally mirror images of each other – the same way your left hand and right hand are mirror images of each other – which, makes them enantiomers.  While they have the same molecular weight and formula (C17H23NO), because their atoms are oriented differently in three-dimensional space, levorphanol and dextrorphan each may have a unique effect on the human body, and are classified as two different drugs.  However, these structural similarities make levorphanol analytically indistinguishable from dextrorphan in most specimen types, using today’s science.  Even though PremierTox already has advanced analytical processes through UPLC-MS/MS for isolating isomers of certain compounds – such as, d- and l- isomers of methamphetamine – there are no viable analytical methods available today for detecting levorphanol separately from dextrorphan.  

Despite their structural similarities, these compounds have significantly different biological effects. Levorphanol is an opiate analgesic that is used to treat moderate to severe pain.  It was approved for use in 1953 as an alternative to morphine, and designated as a Schedule II narcotic.  Levorphanol is 4 to 8 times more potent than morphine and has a significantly longer duration of pain relief.  It does not produce the strong euphoric effects like many other opiates, thus lowering its potential for abuse.  Because of its decreased use over the years, levorphanol is often referred to as the forgotten opioid.  

Dextrorphan (DXO), on the other hand, is a metabolite of dextromethorphan (DXM), a commonly used antitussive in OTC cough medications.  DXM was approved in 1958 by the FDA as a nonaddictive substitute for codeine.  DXO acts by inhibiting NMDA receptors and preventing the reuptake of norepinephrine. This gives it a neuropathic pain reducing quality while alternately interfering with normal communication between multiple areas of the brain.  When abused, DXO can produce euphoric or PCP-like dissociative effects.  Brain lesions have been observed in lab rats from over-exposure.  Pain relieving acetaminophen is often added in OTC brands to enhance efficacy; its potential side effects may help to also prevent recreational use.  There are currently over 100 OTC formulations containing DXM.

Effective June 8, testing for levorphanol/dextrorphan may be ordered as 139 – Levorphanol / Dextrorphan.  A positive result will indicate the presence of one or both drugs indiscriminately.  Providers may further clarify a positive result through any number of means at their discretion, including: a careful interview of the patient, a review of their current medications - including over the counter medications - pill counts, or past history.  The 139 – Levorphanol / Dextrorphan test may be ordered by the provider, per medical necessity, when either drug is prescribed, or when illicit use is suspected.  

If you have any questions regarding this important update, please contact PremierTox Customer Service at any time: 877-412-8330.

References:
  1. Levorphanol: Revisiting an Underutilized Analgesic. Palliative Care: Research and Treatment. 2014 8: (7-10).
  2. Levorphanol: The Forgotten Opioid. Support Care Cancer. 2007 15(3): (259-264).
  3. Levorphanol use: past, present and future. Postgrad Med. 2016 Jan; 128(1): (46-53).
  4. From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Test. and Analysis. 2014 6(7-8): (614-632).
  5. Comparison of the Effects of Dextromethorphan, Dextrorphan, and Levorphanol on the Hypothalamo-Pituitary-Adrenal Axis: The J. of Pharmacology And Experimental Therapeutics. 2004 May; 309(2): (515-522). 
  6. Psychotropic Effects of Dextromethorphan are Altered by the CYP2D6 Polymorphism: A Pilot Study.  J. of Clinical Psychopharmacology. 1998 Aug; 18(4): 332–337.
  7. Abuse of Dextromethorphan. Archives of Family Medicine. 1999 8: (99).
  8. Treatment of Neuropathic Pain. The Clinical J. of Pain. 2002 18(4): S1-S11.
  9. By Johnny-ibn-roomee - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=56612653

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