Statins have been reported to be beneficial in treating a multitude of disorders including dementia due to Alzheimer disease (AD) and vascular dementia (VaD) with varying yet-to-be determined mechanism of actions. Although cholinesterase inhibitors (ChEIs) are still recommended as the primary drug of choice for AD and related diseases, their efficacy is frequently questioned. We recently reported that the 7-neuronal acetylcholine nicotinic receptor (7-nAChR)-mediated neurogenic vasodilation of porcine cerebral arteries was blocked by ChEIs, and this blockade was prevented by statin pretreatment. The exact mechanism of interaction between ChEI and statins remain unclear. It has been shown that activation of the 7-nAChRs located on perivascular postganglionic sympathetic nerve terminals releases norepinephrine, which then acts on presynaptic ₂-adrenoceptors located on the neighboring nitrergic nerve terminals, resulting in release of nitric oxide and vasodilation. The present study, therefore, was designed to determine if the interaction of ChEI and statins occurred at the 7-nAChR level. We examined effects of concurrent application of ChEIs and statins on 7-nAChR-mediated inward currents in primary neuronal cultures of rat superior cervical ganglion cells, the origin of the perivascular sympathetic innervation to the cerebral arteries. The results indicated that physostigmine, neostigmine and galantamine in a concentration-dependent manner inhibited choline- and nicotine-induced whole cell currents. This inhibition, which was non-competitive in nature, was prevented by concurrent application of mevastatin and lovastatin in a concentration-dependent manner. Together, these results suggest that statins protect the 7-nAChR function directly at the receptor level. Since the 7-nAChR is neuroprotective having beneficial effects on memory and cerebral vascular function, its functional inhibition by ChEI may in part explain the limitation of its effectiveness in AD and VaD therapy. Protection of 7-nAChR function from ChEI inhibition by concurrent administration of statins may provide an alternative strategy in improving the efficacy of AD and VaD therapy.