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Several preclinical and clinical studies suggested that tramadol has a multi-mechanistic analgesic action. Upon in vitro evaluation, tramadol parent drug was determined to have only very weak affinity for opioid receptors. Metabolism via CYP2D6, though, yields the O-desmethyl metabolite (M1), which has much greater opioid receptor affinity. In tests in animals and human volunteers, tramadol’s analgesic effect is only partially blocked by the opioid antagonist naloxone. Yet the contribution of parent drug to analgesia is still debated. Observance of good analgesic response to tramadol in Japanese and other Asian populations that express the CYP2D6*10 genotype suggests that parent drug accounts for the majority of tramadol’s analgesic effect in most clinical settings. Understanding of tramadol’s multi-mechanistic action continues to form the basis for understanding its clinical attributes

pharmacology and pharmacy

Tramadol in Japanese Population: the Relative Contribution of M1 Metabolite as Assessed by &amp;lt;i&amp;gt;CYP&amp;lt;/i&amp;gt;2&amp;lt;i&amp;gt;D&amp;lt;/i&amp;gt;6&amp;lt;/i&amp;gt;*10 Genotype