Loading...
Impaired working memory, a core feature of schizophrenia, is not significantly improved by clozapine or other antipsychotics and is hypothesized to occur partly via both abnormal cholinergic transmission in schizophrenia and the anticholinergic burden of medications. Clozapine antagonism at muscarinic M1, M3, and M5 receptors is thought to detrimentally affect cognition. Because clozapine and its metabolites have different and sometimes opposing effects on cholinergic transmission, investigators examined whether a high ratio of clozapine to its major metabolite N-desmethylclozapine (NDMC), a strong partial muscarinic agonist, might harm working memory.
Thirty clinically stable patients with schizophrenia who were taking clozapine at doses th…