EFFICACY OF CLOZAPINE COMPARED WITH OTHER ANTIPSYCHOTICS IN PREVENTING NMDA-ANTAGONIST NEUROTOXICITY

The focus of this article will be on toxic symptoms associated with bl ockade of the N-methyl-D-aspartate (NMDA) subtype of the glutamate rec eptor. We have been studying two parallel phenomena: NMDA-antagonist n eurotoxicity (NAN) in rats and NMDA-antagonist psychotogenicity (NAP) in humans. These phenomena have a common denominator-NMDA receptor hyp ofunction, which is putatively a mechanism operative in schizophrenia. We have found that the NAN reaction in rats can be prevented by speci fic drugs that prevent NAP in humans and by certain antipsychotic agen ts, including clozapine, that ameliorate symptoms in schizophrenia. By studying mechanisms by which clozapine prevents the NAN reaction in r ats, we hope to gain insight into mechanisms by which clozapine or oth er atypical antipsychotics ameliorate symptoms in schizophrenia.