Multi-targeted Ligands for Pain Relief: Analgesic Properties of Dual Opioid/Neurotensin Peptides

The management of pain remains one of the most challenging issues of the 21st century, affecting over a third of the global population, and yet it is often not treated appropriately. The gold standard for the management of moderate to severe pain is to target the µ-opioid receptor (MOP) with opioid ligands such as morphine or fentanyl. Paradoxically, these opioids can lead to serious side effects and even addiction. To address this important public health issue, dual-target ligands that can engage more than one receptor and exert complementary analgesic actions represent an exciting avenue for the treatment of acute and chronic pain.1 Indeed, targeting two or more endogenous nociceptive systems often results in a synergistic or additive effect, thus improving the analgesic/adverse effect ratio.2 Therefore, ligands acting on the neurotensin receptor type 2 (NTSR2), which exert non-opioid antinociceptive effects, provide an attractive option for being fused to an opioid pharmacophore.3