O-Desmethyltramadol

O-Desmethyltramadol is an opioid analgesic and the main active metabolite of tramadol.

(+)-O-Desmethyltramadol is the most important metabolite of tramadol produced in the liver after tramadol is consumed. This metabolite is considerably more potent as a μ opioid agonist than the parent compound.

Tramadol is demethylated by the liver enzyme CYP2D6 in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 ("poor metabolisers") will tend to get reduced analgesic effects from tramadol.

The two enantiomers of O-desmethyltramadol show quite distinct pharmacological profiles; both (+) and (-)-O-desmethyltramadol are inactive as serotonin reuptake inhibitors, but (-)-O-desmethyltramadol retains activity as a noradrenaline reuptake inhibitor and so the mix of both the parent compound and metabolites produced contributes significantly to the complex pharmacological profile of tramadol.