9-Aminoacridine and tacrine differ from other potent channel blockers of NMDA receptors because their binding prevents channel closing and agonist dissociation. The specific properties that determine this mechanism of action remain unknown. In the present work, we studied the action of dicationic analogs of 9-aminoacridine and other tricyclic compounds on the native NMDA receptor in hippocampal pyramidal neurons of rat brain. All the drugs induced a voltage-dependent block of NMDA receptor channels. At -80 mV, they demonstrated IC₅₀ values from 1 to 50 μM. Dicationic compounds had the same voltage dependence as the monocationic ones. Both mono- and dicationic threecyclic compounds are weak blockers of AMPA receptor channels. Thus, they differ significantly from the derivatives of adamantane, di- and triphenyl, for which it has been demonstrated that dicationic analogs are more voltage-dependent NMDA receptor channel blockers then the monocationic analogs. Additionally, the dicationic derivatives of adamantane, di- and threephenyl are the potent antagonists of AMPA receptor channels. The threecyclic compounds including dicationic analogs of 9-aminoacridine differ from 9-aminoacridine by the mechanism of block because they do not prevent NMDA receptor channel from closing. It is concluded that the site of action of 9-aminoacridine on the NMDA receptor channel has specific organization and is very selective for the ligand structure.