Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity.
Antagonists of the N-methyl-D-Aspartate (NMDA) subtype of glutamate receptor (e.g., phencyclidine, ketamine, MK-801) cause a schizophrenia-like psychosis in humans and neurotoxicity in the adult rat brain. We report here that clozapine and structurally related agents (olanzapine, fluperlapine, loxapine, amoxapine) can prevent NMDA antagonist neurotoxicity in the rat with a rank order corresponding to their ability to mimic the antipsychotic properties of clozapine.
Farber
N B
NB
Department of Psychiatry, Washington University School of Medicine, St.Louis, MO 63110, USA.
Foster
J
J
Duhan
N L
NL
Olney
J W
JW
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D003989:Dibenzoxazepines / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D005260:Female; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009420:Nervous System / Q000187:drug effects; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D014150:Antipsychotic Agents; D003984:Dibenzazepines; D003989:Dibenzoxazepines; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D010890:Pirenzepine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C041528:fluperlapine; D003024:Clozapine; D000077152:Olanzapine