TAN-452 is an orally active, selective peripherally acting δ-opioid receptor (DOR) antagonist with a K i of 0.47 nM and a K b of 0.21 nM. TAN-452 is an antagonist for μ-opioid receptor ( MOR ; K i =36.56 nM and K b =9.43 nM) and κ-opioid receptor ( KOR ; K i =5.31 nM and K b =7.18 nM). TAN-452, a derivative of Naltrindole, demonstrates low brain penetrability and attenuates morphine-induced side effects without affecting pain control.