Bis(9)-(−)-nor-meptazinol as a novel dual-binding AChEI potently ameliorates scopolamine-induced cognitive deficits in mice

► Bis(9)-(−)-nor-meptazinol(Bis-Mep) is shown to be a dual-binding AChE inhibitor. ► Two “water bridges” help Bis-Mep stabilize its dual-binding on AChE. ► Bis-Mep (s.c) shows significant cognitive amelioration at 100 ng/kg in mice. ► Bis-Mep exhibits its potent AChE inhibition in mice brain.