Published: February 21, 2019 | By Sydney Valentino
Friday, June 29, 2018 – Mitra Shokrollahi (BSc, MA), an MSc. candidate at FARNCOMBE Family Digestive Health Research Institute, Department of Medicine (supervisor Dr. Jan Huizinga), delivered a research proposal on:
“Potential Effects of a Novel 5-HT4 Receptor Agonist for Early Stage Alzheimer’s Disease Dementia”
Following, Mitra summarized the take-home points of her talk…
- 5-HT4 receptor agonists are used to increase gastrointestinal (GI) prokinetic activity. My MSc. thesis research in the Huizinga lab is on the effects of intraluminal “prucalopride”, a highly selective 5-HT4receptor agonist, on GI motility.
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However, there is also evidence that 5-HT4 receptor agonists can be used in treating dementias due to cholinergic deficits such as Alzheimer’s disease (AD) dementia.
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It is well known that about 30% of individuals with Mild Cognitive Impairment (MCI) convert to early stages of AD dementia. Therefore, early stage treatment is of paramount importance.
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Studies demonstrate that prucalopride increases acetylcholine levels and hippocampal θ oscillation power in the rat prefrontal cortex resulting in pro-cognitive effects.
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In the rat prefrontal cortex, prucalopride also potentiates the acetylcholine increase caused by the acetylcholinesterase inhibitor “donepezil”, a currently used pharmacotherapy for AD dementia.
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A novel highly selective 5-HT4 receptor agonist YH12852 has been shown to be more effective than prucalopride in evoking prokinetic effects in the GI tract.
- Therefore, it is possible that at the early stages of a disease, YH12852 could be a more effective alternative therapeutic agent for AD compared to other 5-HT4receptor agonists.
Please feel free to contact Mitra Shokrollahi (shokorlm@mcmaster.ca) if you have any questions or would like to discuss future work.
This blog post was first published by the MIRA Trainee Network. Read the ​original article.​​
