Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants

Abstract

Our results suggest that O-desmethyltramadol binding to μ-opioid receptor on the chemoreceptor trigger zone is responsible for inducing emetic response in tramadol treatment. This interpretation is supported by a previous finding that μ-opioid receptor has a higher affinity for O-desmethyltramadol than for tramadol or other metabolites. Although our findings need to be confirmed in larger populations to be used as pharmacogenetic prediction of tramadol toxicity, high-activity genotypes of CYP2D6 and a high-expression genotype of OPRM1 appear to confer high risk of nausea/vomiting in tramadol treatment.