Designing Safer Analgesics via μ-Opioid Receptor Pathways

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. It is therefore imperative that both academia and industry develop novel μOR analgesics which retain their opioid analgesic properties but with fewer or no adverse effects. In this review we outline recent progress towards the discovery of safer opioid analgesics. Pain is a major clinical and economic problem. Owing to the serious side effects associated with current painkillers, the discovery of less toxic medications is an imperative in both academia and industry. Owing to recent advances in computational and structural biology, several μOR-mediated painkillers with fewer side effects have been successfully designed.