25E-NBOMe, a novel psychoactive substance, induces conditioned place preference in male mice and self-administration in male rats, indicating abuse potential. The drug enhances dopamine transporter and dopamine D1 receptor expression in the nucleus accumbens, reduces dopamine levels, and activates intracellular signaling pathways. Blocking the D1 receptor or inhibiting D1 receptor-expressing neurons attenuates the conditioned place preference. The drug also produces hallucinogenic effects via serotonin 2A receptor activity, as shown by the head twitch response. These findings suggest that D1 receptor signaling may govern the addictive potential of 25E-NBOMe.
Microdosing studies, which use subpharmacological doses of drug candidates, offer early information on how the body processes these compounds, potentially reducing costs and improving productivity in early clinical drug development. Highly sensitive analytical technology, particularly accelerator mass spectrometry (AMS), enables qualitative and quantitative assays of labeled compounds in humans, providing pharmacokinetic and metabolic data for candidate selection. The applicability of microdosing is expanding into absolute bioavailability and mass balance studies. It remains uncertain whether microdosing adequately predicts therapeutic-dose pharmacokinetics, but further development of AMS-based microdosing may benefit drug development and pose new challenges for researchers. Introducing this method in Korea could enhance competitiveness in pharmaceutical research and development.