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Development of Gαi protein selective μ opioid receptor analgesics to limit side‐effects

The clinical utility of opioids as analgesics is limited by their serious side effects, which include respiratory inhibition, gastrointestinal motility disorders, tolerance and addiction. Opioids act by binding to μ opioid receptors (MORs) to trigger G‐protein and β‐arrestin‐mediated signaling cascades. The Gαi class of G‐protein is thought to play an important role in transducing the analgesic actions of opioids. Gαi subunits include Gi1, Gi2, Gi3, Go and Gz. In addition, Gβγ subunits also contribute to the actions of opioids, and the many subtypes of Gβγ subunits adding yet more complexity to MOR‐mediated signaling.