The dose-response relationship for memory impairment by anticholinergic drugs

Twelve stabilized chronic schizophrenic outpatients receiving maintenance treatment with fluphenazine decanoate plus anticholinergic antiparkinsonian drugs underwent two challenge sessions receiving, in random sequence and double-blind, injections of either benztropine or glycopyrrolate (a peripherally active anticholinergic agent that penetrates the CNS poorly, used as an active placebo). Performance on free recall testing was significantly worse after benztropine than after glycopyrrolate. It has previously been shown that routine clinical doses of anticholinergic antiparkinsonian drugs impair verbal learning relative to a drug-free baseline. Our results suggest that memory impairment continues to further increase as anticholinergic drugs are pushed to the upper limit of the acceptable clinical range.