Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile

Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecular modeling. In addition, contilisant significantly restores the cognitive deficit induced by Aβ in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.
J.M.-C. thanks MINECO (Grant SAF2015-65586-R), UCJC (Grants 2015-12, 2014-35, and 2015-21), and EU (COST Action CA15135) for support. J.M.-C. thanks Prof. Stark and Prof. Ramsay, as well as Prof. Jia (Beijing Normal University), Dr. Chioua (CSIC), and Dr. Romero (UCM) for their help and support.