Why an M1 Antagonist Could Be a More Selective Model for Memory Impairment than Scopolamine

Since the early studies of Deutsch (1), the non-selective muscarinic receptor antagonist scopolamine has been used as a drug that impairs memory performance in man. The notion that scopolamine could be used as a pharmacological model of age-associated memory impairment and dementia further strengthened the cholinergic hypothesis of geriatric memory dysfunction by Bartus et al. (2). Since then, a vast amount of studies applied this model to induce memory impairments in young healthy subjects to model age-related memory disorders. At present, scopolamine is still considered to be the best model for inducing cognitive impairments in healthy subjects (3). Scopolamine is therefore used as a pharmacological model to test novel cognition-enhancing drugs in animals [e.g., Ref. (4–6)] and in humans [e.g., Ref. (7, 8)]. In clinical trials, scopolamine is in particular being used as a model for AD in which novel cognition-enhancing drugs are tested (see https://ClinicalTrials.gov).