Contilisant, a Tetratarget Small Molecule for Alzheimer’s Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition and H3R Antagonism with Sigma 1R Agonism Profile

Contilisant, a Tetratarget Small Molecule for Alzheimer’s Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition and H3R Antagonism with Sigma 1R Agonism Profile

Bautista-Aguilera, O. M.; Budni, J.; Mina, F.; Medeiros, E. B.; Deuther-Conrad, W.; Entrena, J. M.; Moraleda, I.; Iriepa, I.; López-Muñoz, F.; Marco-Contelles, J.

Abstract

Contilisant, a permeable, antioxidant and neuroprotectant agent, showing high nM affinity at H3R, 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 Aβ1-42 in the radial maze assay in an in vivo Alzheimer’s disease test, comparing very favorably with donepezil.

Keywords: Alzheimer’s disease; Aβ; ASS234; ChE inhibitor; Contilisant; Cognitive impairment; H3R antagonist; MAO inhibitor; Molecular modeling; Radial arm-maze test; hSigma 1R agonist; rVAChT modulator; Y-maze test

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