N,O-Didesmethyltramadol (tramadol metabolite M5) is an opioid derivative which is one of two active metabolites of the opioid analgesic medication tramadol. It is many times less potent than the other active metabolite O-Desmethyltramadol but is still more potent as a mu opioid receptoragonist than tramadol itself, unlike the other metabolites N-desmethyltramadol, N,N-didesmethyltramadol, and N,N,O-tridesmethyltramadol which are entirely without opioid activity.[1][2][3][4] As with tramadol and O-desmethyltramadol it is found as a mixture of the (1S,2S)- and (1R,2R)-enantiomers, although the separate enantiomers of N,O-didesmethyltramadol have not been studied individually. It is specifically listed as a Schedule I drug in Canada,[5] presumably due to concerns it may be subject to abuse as a designer drug in a similar manner to other opioid active metabolites such as O-desmethyltramadol and nortilidine.
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^DePriest AZ, Puet BL, Holt AC, Roberts A, Cone EJ (July 2015). "Metabolism and Disposition of Prescription Opioids: A Review". Forensic Science Review. 27 (2): 115–145. PMID26227254.
^Barbosa J, Faria J, Queirós O, Moreira R, Carvalho F, Dinis-Oliveira RJ (November 2016). "Comparative metabolism of tramadol and tapentadol: a toxicological perspective". Drug Metabolism Reviews. 48 (4): 577–592. doi:10.1080/03602532.2016.1229788. PMID27580162.
