Related Experiment Video
Updated: Jul 14, 2025

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats
Published on: March 17, 2019
Superiority of the Triple-Acting 5-HT6R/5-HT3R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT6R
Katarzyna Grychowska1, Uriel López-Sánchez2, Mathieu Vitalis3
1Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Str., 30-688 Kraków, Poland.
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 intracerebroventricular injection of an oligomeric solution of amyloid-β peptide (oAβ) in the T-maze test in rats. PZ-1922, but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAβ. These data support the potential of a multitarget approach involving the joint modulation of 5-HT6R/5-HT3R/MAO-B in AD.
Related Concept Videos
Antidepressant Drugs: MAOIs and Other Agents
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Drugs Affecting Neurotransmitter Release or Uptake
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Antipsychotic Drugs: Typical and Atypical Agents

