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 μ opioid receptor 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 adverse effects. These include biased agonism, opioids targeting multiple receptors, allosteric modulators, heteromers and splice variants of the μ receptor. This review will focus on the current status of the field and some upcoming targets of interest that may lead to a safer next generation of analgesics. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.