Dicyclomine (Dicycloverine) is a potent, orally active antagonist of muscarinic cholinergic receptors, specifically M1 and M2 subtypes, with Ki values of 5.1 nM and 54.6 nM in brush-border and basal plasma membranes, respectively [1] [2]. As an antispasmodic agent, it relieves smooth muscle spasm of the gastrointestinal tract in vivo.

Intraperitoneal injections of Dicyclomine (Dicycloverine), administered daily at doses of 2.0, 4.0, and 8.0 mg/kg for a week, significantly impaired cognitive performance and memory in C57Bl/6 mice, with a pronounced effect observed in the paired-associates learning (PAL) task. Notably, at the highest dosage (8 mg/kg), Dicyclomine exacerbated cognitive impairments across all measurements. Furthermore, 3xTg-AD mice treated with Dicyclomine displayed worse memory impairments than NonTg mice treated similarly. Lower doses also led to behavioral impairments in spatial tasks, suggesting that Dicyclomine's detrimental effects on cognition result from its actions beyond the hippocampus.