• Thien C Pham, Jeffrey Fudin, and Robert B Raffa.
• PGY2 Pain and Palliative Care Pharmacy Residency, Stratton VA Medical Center, Albany, New York, USA.
• Pain Med. 2015 Sep 1; 16 (9): 1673-9.

BackgroundMethadone has been a stalwart pharmacologic option for the management of opioid drug dependence for many years. It substitutes for opioid agonists and possesses certain pharmacokinetic properties that confer characteristics preferable to those of other opioids for this application. Methadone is likewise used as an option for the treatment of pain, particularly chronic pain. It has a spectrum of pharmacodynamic activity, including contributions from non-opioid components, that translates to its specific clinical attributes as an analgesic. Unfortunately, basic science studies and accumulated clinical experience with methadone have revealed some undesirable, and even worrisome, features, including issues of safety. The benefit/risk ratio of methadone might be acceptable if there was no better alternative, but neither its pharmacokinetic nor pharmacodynamic properties are unique to methadone.ObjectiveWe review the basic and clinical pharmacology of methadone and suggest that levorphanol should receive attention as a possible alternative.ConclusionUnlike methadone, levorphanol is a more potent NMDA antagonist, possesses a higher affinity for DOR and KOR, has a shorter plasma half-life yet longer duration of action, has no CYP450 interactions or QTc prolongation risk, can be a viable option in the elderly, palliative care, and SCI patients, requires little to no need for co-administration of adjuvant analgesics, and has potentially a lower risk of drug-related Emergency Department visits compared to other opioids.Wiley Periodicals, Inc.

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