The anomalous pharmacology of fentanyl

Fentanyl is a key therapeutic, used in anaesthesia and pain management. It is alsoincreasingly used illicitly and is responsible for a large and growing number of opioidoverdose deaths, especially in North America. A number of factors have beensuggested to contribute to fentanyl's lethality, including rapid onset of action, in vivopotency, ligand bias, induction of muscle rigidity and reduced sensitivity to reversalby naloxone. Some of these factors can be considered to represent ‘anomalous’pharmacological properties of fentanyl when compared with prototypical opioidagonists such as morphine. In this review, we examine the nature of fentanyl's‘anomalous’ properties, to determine whether there is really a pharmacological basisto support the existence of such properties, and also discuss whether such propertiesare likely to contribute to overdose deaths involving fentanyls.