Tacripyrines have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are aimed to develop a multitarget therapeutic strategy to confront Alzheimers disease.Tacripyrines are selective and potent AChE inhibitors in the nanomolar range.The mixed type inhibition of hAChE activity of p-methoxytacripyrine (IC50 105 ± 15 nM) is associated to a 30.7 ± 8.6% inhibition of the proaggregating action of AChE on the Aβ and a moderate inhibition of Aβ self-aggregation (34.9 ± 5.4%).Molecular modelling indicates that binding of pmethoxytacripyrine to the AChE PAS mainly involves the (S)-enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by this compound.Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the BBB, emerging as lead candidates for treating AD.