20.03.5.5 Tramadol

Tramadol is a weak agonist at μ-receptors. The demethylated metabolite of tramadol is more potent than tramadol at stimulating μ-receptors. Thus, the metabolite will contribute to the analgesic effect of tramadol. Tramadol also inhibits the serotonin transporter (SERT) and noradrenaline transporter (NET) to increase the levels of 5-HT and noradrenaline, respectively, in the brain (Figure 20.11). It has been postulated that this 5-HT and noradrenaline may contribute to analgesic effect of tramadol.

Figure 20.11 Mechanisms of action of tramadol (Copyright Sheila Doggrell, QUT)

Tramadol is used orally (where it has a 68% bioavailability) or intramuscularly (100% bioavailability). It is used in the treatment of mild-to-moderate pain, which is step 2 of Figure 20.8. Tramadol is not as effective as morphine for the treatment of severe pain (step 3).