2099681-31-7

AT-121 is a dual μ-opioid and nociceptin receptor partial agonist (K_is = 16.49 and 3.67 nM, respectively).¹ It stimulates [³⁵S]GTPγS binding to cell membranes expressing μ-opioid or nociceptin receptors (EC₅₀s = 19.6 and 34.7 nM, respectively). AT-121 (0.003-0.03 mg/kg) decreases capsaicin-induced thermal allodynia without increasing scratching activity in rhesus monkeys in a dose-dependent manner. It lacks reinforcing effects, a marker of abuse potential, and reduces oxycodone, but not food pellet, reinforcement in a drug self-administration assay in rhesus monkeys when administered at doses ranging from 0.3 to 10 μg/kg per injection. AT-121 (0.01 or 0.03 mg/kg) does not induce hyperalgesia, a marker of tolerance development, in rhesus monkeys.

1. Ding, H., Kiguchi, N., Yasuda, D., et al. A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates Sci. Transl. Med. 10(456),eaar3483(2018).