2-Aminoindan and its Ring-Substituted Derivatives Interact with Plasma Membrane Monoamine Transporters and α2-Adrenergic Receptors
Psychopharmacology March 1, 2019 A. Halberstadt, S. Brandt, D. Walther et al.
A class of designer drugs derived from 2-aminoindan (2-AI) interacts with monoamine transporters in ways that predict distinct psychoactive effects. 2-AI itself acts as a selective substrate for norepinephrine and dopamine transporters, suggesting (+)-amphetamine-like effects and abuse potential. Adding ring substitutions increases potency at the serotonin transporter while reducing potency at dopamine and norepinephrine transporters. Among the derivatives, MMAI is highly selective for the serotonin transporter, with 100-fold lower potency at norepinephrine and dopamine transporters, while MDAI and 5-MeO-AI show moderate serotonin selectivity. The compounds also bind to α2-adrenoceptor subtypes, with 2-AI having highest affinity for α2C receptors (Ki = 41 nM). Ring-substituted derivatives may produce MDMA-like effects with less abuse liability.