Superiority of the Triple-Acting 5-HT₆R/5-HT₃R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT₆R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats.

ABSTRACT: The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HT₆R antagonism and interaction with 5-HT₃R were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable PZ-1922 reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HT₆R antagonist) in the AD model, which involved i

SUBMITTER: Grychowska K 

PROVIDER: S-EPMC10641814 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature