Strategies towards safer opioid analgesics - a review of old and upcoming targets.

Opioids continue to be of use for the treatment of pain. Most clinically used analgesics target the mu opioid receptor (MOR) whose activation results in adverse effects like respiratory depression, addiction, and abuse liability. Various approaches have been used by the field to separate receptor mediated analgesic actions from its adverse effects. These include biased agonism, opioids targeting multiple receptors, allosteric modulators, heteromers, and splice variants of the MOR. This review will focus on the current status of the field and some upcoming targets of interest which may lead to a safer next generation of analgesics.