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Toxicology Through a Looking Glass: Stereochemical Questions and Some Answers
Published in Steven H. Y. Wong, Iraving Sunshine, Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
The victim lay dead in the living room—the only clue, a bottle of cough medicine. It is up to Dr. Kay Scarpetta, Chief Medical Examiner of Richmond, Virginia, to solve the mystery, and the answer lies in a three-dimensional understanding of pharmacology and toxicology. Dr. Scarpetta reveals the solution to Police Lieutenant Marino in the following manner: ”The active ingredient in the cough suppressant we found in Miss Harper’s bathroom is dextromethorphan, an analogue of codeine. Dextromethorphan is benign unless you ingest a tremendous dose. It’s the d-isomer of a compound, 3-methoxy-N-methylmorphinan.There’s another drug that is the l-isomer of this same compound that dextromethorphan is the d-isomer of. The l-isomer compound is levomethorphan, a potent narcotic about five times stronger than morphine. And the only difference between the two drugs as far as detection goes is that, when viewed through an optical rotatory device called a polarimeter, dextromethorphan rotates (plane polarized) light to the right and levomethorphan rotates (plane polarized) light to the left.””In other words without this contraption you can’t tell the difference between the two drugs,” Marino concluded.”Not in the tox tests routinely done. Levomethorphan comes up dextromethorphan because the compounds are the same. The only discernible difference is they bend (plane polarized) light in opposite directions….”1
Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects
Published in Drug Metabolism Reviews, 2020
Ana Rita Silva, Ricardo Jorge Dinis-Oliveira
DXM (3-methoxy-N-methylmorphinan; Figure 1) is the dextrorotatory [d- or (–)] enantiomer of levomethorphan [l- or (+)], which is the methyl ether of DXO (3-hydroxy-N-methylmorphinan) and levorphanol, respectively (Sromek et al. 2014). Although former levorotatory compounds are both opioid analgesics, only levorphanol was clinically developed (Gudin et al. 2016; Le Rouzic et al. 2019). Moreover, levorphanol is the levorotatory isomer of racemic 3-hydroxy-N-methylmorphinan (Dromoran®) and named as Levo-Dromoran®. DXM is named according to IUPAC rules as (+)-3-methoxy-17-methyl-9α,13α,14α-morphinan. It is also the d-isomer of methorphan (racemic mixture), but unlike the l-isomer, it does not have opioid activity. Methorphan presents as two isomeric forms, each with differing pharmacology and effects with respect to its two enantiomers. The DXM is used as an antitussive drug in cough medicines (and in high doses, it is a dissociative hallucinogen), whereas the levorotatory enantiomer levomethorphan, a prodrug of levorphanol, is a strong opioid analgesic that is listed as a schedule II drug in the USA (Wong and Sunshine 1996; Bortolotti et al. 2013; Gudin et al. 2016). Levorphanol binding affinity for the mu (MOR; µ) opioid receptor, 0.42 nM, is greater than the affinity of morphine, 1.24 nM and also presents longer t1/2 (Bortolotti et al. 2013). As DXM is approved for use in OTC drugs, accurate control of enantiomeric purity is essential to assure that commercial DXM preparations do not contain the l-enantiomer.
Trends in dextromethorphan cough and cold products: 2000–2015 National Poison Data System intentional abuse exposure calls
Published in Clinical Toxicology, 2018
Sara Karami, Jacqueline M. Major, Silvia Calderon, Jana K. McAninch
Dextromethorphan (DXM) was approved by the United States (U.S.) Food and Drug Administration (FDA) in 1958 for use as a non-prescription cough medication [1]. Currently, DXM is available as tablets, capsules, lozenges and syrups, in a variety of prescription and over-the-counter (OTC) cough and cold remedies, either alone or in combination with other ingredients like analgesics, antihistamines and expectorants [1]. DXM is the d-isomer of levomethorphan, a semisynthetic morphine derivative; yet, DXM does not act as a mu-receptor agonist or have analgesic properties [2]. At supratherapeutic doses, DXM can cause euphoria, hallucinations and dissociative sedation [3].