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Narcotic Analgesics And Antagonists
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
N-Methylmorphinan can be looked at as a molecule of morphine from which the allylic alcohol moiety, the oxygen bridge and the phenolic hydroxyl group have been removed. Nevertheless, it retained one-fifth of the analgesic activity of morphine. This is a B/C ds-fused compound, as is morphine. The trans-fused diastereomeric N-methylisomorphinan is practically devoid of analgesic activity. When the phenolic hydroxyl group is incorporated in the molecule, to form racemorphan (dl-3-hydroxy-N-methylmorphinan, see Formula 27)49–51 the analgesic potency becomes twice that of morphine in man. Thus, neither the presence of an oxygen bridge nor the allylic alcohol portion of morphine is necessary for its analgesic activity. The optical resolution of racemorphan, followed by etherification in the case of the dextro isomer, resulted in two clinically useful drugs; the analgesically active levorphanol (/evo-3-hydroxy- N-methylmorphinan, levo, Formula 27) and the nonanalgesic, antitussive dextromethorphan1 (dextro-3-methoxy-N-methyl-morphinan, Formula 28).
Pharmacokinetics and pharmacodynamics of dextromethorphan: clinical and forensic aspects
Published in Drug Metabolism Reviews, 2020
Ana Rita Silva, Ricardo Jorge Dinis-Oliveira
Therefore, DXM is chemically an opium alkaloid derivative but since it does not act pharmacologically at opioid receptors, it is not an opioid and does not have analgesic, euphoriant, and respiratory depression effects, such as codeine and morphine (Bem and Peck 1992; Jasinski 2000; Pechnick and Poland 2004). In other words, DXM and DXO, both dextrorotatory enantiomers, are non-opioid opium alkaloid derivatives. Racemethorphan is the racemic mixture composed by the two enantiomers DXM and levomethorphan (Wong and Sunshine 1996). Racemorphan or morphanol refers to the racemic mixture of DXO and levorphanol, both with pharmacological and toxicological effects similar to their correspondent methyl ether derivatives (Aumatell and Wells 1993). This enantiomeric behavior is characteristic of other opioids. Indeed, dextrorotatory opioids have very different pharmacological profiles than their levorotatory isomers. Unlike the levorotatory opioids, dextrorotatory generally have little or no affinity to the mu (MOR; µ), delta (DOR; δ), or kappa (KOR; Κ) opioid receptors, and thus do not carry the same abuse and addiction potential as their levorotatory enantiomers (Sromek et al. 2014). Dextrorotatory enantiomers typically act as weak to moderate noncompetitive NMDA receptor antagonists and have affinity to the σ1 and α3β4 nicotinic receptors (Glick et al. 2001). Both dextrorotatory and levorotatory opioids have antitussive properties.