Molecular characterization and comparison of the effects of several opioid agonists clinically used in Japan - Using the CellKey™ and internalization assays with stable cells expressing opioid μ, δ or μ/δ dimerized receptors

Morphine(MRP), fentanyl(FEN), oxycodone(OXY) and hydromorphone(HDM) are approved as opioid analgesics in Japan, and they show analgesia mainly through activation of μ opioid receptors (μOR) among μ, δ, and κORs. However, these analgesics show different side effects, possibly due to their distinct intracellular signaling. Recently, it was demonstrated that μOR forms a heterodimer with δOR, and its specific agonist ML335 has been reported to have less side effects and lower tolerance. However, the precise mechanism of ML335 and other opioid analgesics on OR activities are poorly clarified.