Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter-In Silico and In Vitro Exploration of Dissociative Diarylethylamines.
Brain Sciences April 7, 2018 Michelle A Sahai, Colin Davidson, Neelakshi Dutta et al.
Diphenidine (DPH), a dissociative novel psychoactive substance, binds to the dopamine transporter in rat brain tissue and increases electrically-evoked dopamine efflux in the nucleus accumbens, indicating potential for addiction. In contrast, methoxphenidine (MXP) shows no significant effect on dopamine transporter binding or dopamine release. Computational modeling of five dissociative compounds confirms these differences and explains the atomic-level interactions within the dopamine transporter. Despite their chemical similarity, DPH, but not MXP, may have addictive liability through stimulant-like actions on dopamine systems.