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Mellar P. Davis

and Columba Quigley

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date: 17 September 2021

Chapter 13 discusses Methadone, a synthetic opioid agonist which was developed primarily as an analgesic and only later adopted as maintenance therapy for addiction. It is classified as a biphenyl propylamine synthetic potent mu and delta agonist, and is actually a mixture of two enantiomers: the R (L) methadone enantiomer is the mu receptor agonist and the S (D) enantiomer is stated to be the N-methyl-D-aspartate (NMDA) receptor antagonist. However, both enantiomers are NMDA antagonists. Methadone has unique opioid receptor interactions and pharmacokinetics which set it apart from other opioid agonists and contributes to its non-analgesic tolerance to other opioids. These differences also contribute to difficulty in determining equi-analgesia when switching opioids. The significant difference in methadone metabolism between individuals necessitates dosing guidelines for safe use that are distinctly different from other opioids.

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