Norbinaltorphimine dihydrochloride is a selective and potent κ opioid receptor antagonist that induces itch-associated responses in mice.

Norbinaltorphimine dihydrochloride reversibly antagonizes the effects of κ agonists with pA2 values ranging from 10.2 to 10.4. However, it is important to note that Norbinaltorphimine dihydrochloride is much less potent as an antagonist at μ and δ receptors, where the pA2 values are 7.4-7.6 and 7.6-7.8, respectively[3].

In adolescent rats, Norbinaltorphimine dihydrochloride exhibits weak and inconsistent effects on THC-induced taste avoidance. Notably, the impact of Norbinaltorphimine dihydrochloride varies based on dose and trial, as it both attenuates and strengthens taste avoidance. However, these effects are limited, with no significant influence on the final one-bottle avoidance and no observable effects on the two-bottle preference test. Interestingly, Norbinaltorphimine dihydrochloride demonstrates no effect on THC-induced taste avoidance in adult rats as well[2].Furthermore, when administered as a pretreatment,Norbinaltorphimine dihydrochloride significantly attenuates stress-induced reinstatement of nicotine-conditioned place preference (CPP). However, it is important to note that Norbinaltorphimine dihydrochloride has no discernible effect on nicotine-primed reinstatement[1].