The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron.

Tramadol has weak opioid properties, and an analgesic effect that is mediated mainly by inhibition of the reuptake of norepinephrine and serotonin (5-hydroxytryptamine [5-HT]) and facilitation of 5-HT release (1,2) at the spinal cord. Because 5-HT3 receptors play a key role in pain transmission at the spinal level (3), the 5-HT3 antagonist ondansetron may decrease the efficacy of tramadol, as suggested in an abstract by Maroof et al. In that study, a small dose of 1 mg/kg tramadol was administered along with ondansetron 0.