Acetylcholinesterase inhibitors used or tested in Alzheimers disease therapy; their passive diffusion through blood brain barrier: In vitro study

Abstract

Although the information about Alzheimer's disease (AD) etiology is still unclear; acetylcholinesterase inhibitors still play a major role in symptomatic treatment of AD. Unfortunately, a relevant argumentation is complicated since information about real drug concentration in the brain or time-dependent blood-brain barrier (BBB) distribution studies are still quite rare. In this in vitro study, high-performance liquid chromatography (HPLC) method with special (IAM - immobilized artificial membrane) column was used to determine the ability of cholinesterase inhibitors to penetrate through BBB. Set of 8 structurally different cholinesterase inhibitors applicable to AD treatment was evaluated throughout this study. According to our method, all molecules are able to penetrate BBB by passive transport. However, some molecules such as huperzine A and galanthamine have lower ability to penetrate the BBB directly. These molecules may be delivered into the brain via active transport. Other molecules probably use passive transport to permeate into the central nervous system; tacrine and 7-methoxytacrine exert the highest passive permeation from this set of compounds.