N-Methyl-D-aspartate (NMDA) receptor antagonists are perspective candidates for medication development for a number of diseases/states that are associated with increased aggressiveness (e.g., opioid withdrawal). The prototypic NMDA receptor antagonist phencyclidine (PCP) itself is a widely abused substance and is known to elevate levels of aggression in drug users. The present study was aimed at testing several drugs that share with PCP the ability to block NMDA receptor-associated channel. The resident-intruder procedure was used to assess drug effects on aggressive behavior in isolated male mice. Resident aggressive mice were administered NMDA channel blockers (PCP; 0.3-10 mg/kg), dizocilpine (MK-801; 0.01-0.3 mg/kg), memantine (1-30 mg/kg), and MRZ 2/579 (0.1-5.6 mg/kg). The competitive NMDA receptor antagonist DCPPene (0.1-5.6 mg/kg) was also tested as a compound representing an alternative approach to reduce activity of NMDA receptor complex. PCP, dizocilpine, and memantine inhibited expression of aggressive behaviors only at doses that produced ataxia. The novel channel blocker MRZ 2/579 also produced ataxia at the highest dose level but failed to affect aggressiveness. Reduction in aggression with a corresponding increase in sociability was observed after administration of D-CPPene. Overall, the present results suggest that NMDA receptor channel blockers do not exert selective effects on aggressive behavior.