Tramadol: Basic pharmacology and emerging concepts

Tramadol hydrochloride is a widely prescribed, centrally acting analgesic marketed in over 90 countries. Before being released in the U.S. in 1995, the drug had been available in Europe for almost two decades. Thus, the pharmacokinetic and pharmacodynamic properties of tramadol have been extensively investigated. However, additional information about the drug continues to be discovered. Tramadol exists as a racemic mixture with the (+)-enantiomer and the (-)-enantiomer, and at least some of their metabolites, having different effects. Tramadol has dual mechanisms of action by which analgesia may be achieved: micro-opioid receptor activation and enhancement of serotonin and norepinephrine transmission. Serotonin syndrome may occur in patients taking combinations of tramadol and other agents that increase serotonin activity. The relative degree of contribution of each mechanism toward pain control is not fully understood. By increasing serotonin and norepinephrine neurotransmission, tramadol may conceivably also exert a degree of antidepressant effect. Therefore, tramadol may be of particular value in patients with chronic pain who also suffer from depression. This drug has been shown to be beneficial in the treatment of a wide range of acute and chronic pain syndromes, including neuropathic pain. While abuse of tramadol may occur, several large studies have demonstrated that the incidence of abuse is rather low, about one case per 100,000 patients.