The pharmacology of tramadol

Abstract

(+/-)-Tramadol is a central analgesic with low affinity for opioid receptors. The rate of production of its M1 metabolite (O-demethyl tramadol) is influenced by debrisoquine-type polymorphism, and this metabolite shows a higher affinity for opioid receptors than the parent drug. Experimental and clinical data suggest that tramadol may also exert its analgesic effect through direct modulation of central monaminergic pathways. Indeed, after a single oral dose, the role of the mu-receptor agonist component of the antinociceptive effect of tramadol appears to be minor, with most of the analgesic effect being attributable to nonopioid properties of the parent compound. Approximately 2-fold accumulation of the parent compound and the M1 metabolite may be expected during multiple dose treatment. The duration of analgesic effect after a single oral dose of tramadol 100 mg is about 6 hours. Clinical experience has confirmed that tramadol is an effective and relatively safe analgesic that may be of value in several pain conditions not requiring treatment with strong opioids.