Memantine has phencyclidine-like but not cocaine-like discriminative stimulus effects in rats

It has recently been reported that the amantadine derivative, memantine, which is used in the treatment of Parkinsonism, has N-methyl-D-aspartate (NMDA) antagonist properties. In order to investigate whether the behavioural effects of memantine could also be mediated through this mechanism the drug was administered to rats trained to discriminate phencyclidine (3mg/kg) from saline. Memantine produced a dose-related (2.5-10mg/kg) substitution for phencyclidine. Neither amantadine nor cocaine substituted for phencyclidine. In rats trained to discriminate cocaine (10mg/kg) memantine did not substitute. These results show that memantine has phencyclidine-like but not cocaine-like discriminative stimulus effects indicating that the behavioural actions of memantine, like those of phencyclidine, are probably produced by a non-competitive inhibition of NMDA receptors.