Astemizole (Hismanal, Janssen Pharmaceutica) and lansoprazole (Prevacid, Novartis), with medical applications in the treatment of allergies and gastrointestinal disorders respectively, can be used as PET radiotracers for the early detection of Alzheimer's disease, according to a study published in the January issue of the Journal of Alzheimer's Disease.
Astemizole, an over-the-counter (OTC) antihistamine and lansoprazole, an OTC proton pump inhibitor, specifically bind directly to aggregated variants of tau protein and to paired helical filaments isolated from brains of Alzheimer's disease patients, according to the authors. (Of note, astemizole has been removed from the market in most countries because of concerns about serious heart rhythm disturbances when astemizole is taken with other medications or foods that raise the level of astemizole in the blood).
Ricardo B. Maccioni, PhD, from the International Center for Biomedicine in Santiago, Chile, and colleagues assessed the interactions of astemizole and lansoprazole with tau aggregates using radioligand assays, surface plasmon resonance and bioinformatic approaches.
According to Maccioni and colleagues, there was high affinity of astemizole and lansoprazole for tau aggregates and they can be used to tag brain-isolated tau-aggregates and heparin-induced polymers of recombinant tau.
“Importantly, our studies indicate that the brain/blood concentration ratios for these compounds were suitable for their use as PET radiotracers,” wrote Maccioni. The capacity of astemizole and lansoprazole to penetrate the blood-brain barrier was confirmed by the investigators using parallel artificial membrane permeability assays or by pharmacokinetic studies comparing distribution profiles in blood and brain in mice.
“Since neurofibrillary tangles are positively correlated with cognitive impairment, we concluded that astemizole and lansoprazole have a great potential in PET neuroimaing for in vivo early detection of Alzheimer's disease and in reducing the formation of neurofibrillary tangles,” concluded the authors.