Constipation drug can improve memory and cognition

A drug that treats constipation could also be a useful treatment for cognitive problems in patients with mental illness, according to a new study.

Previous animal studies have shown that drugs that target the 5-HT4 receptor are promising for improving cognitive function.

Now researchers at the University of Oxford have tested prucalopride, which is used to treat constipation and which targets the 5-HT4 receptor. They say it may improve cognition.

The small-scale proof-of-concept study involved 44 healthy volunteers, aged 18-36, of whom 23 were given prucalopride, and the remaining 21 were given a placebo.

After six days all the volunteers had an fMRI brain scan and before they entered the scanner, they were shown a series of images of animals and landscapes.

They viewed these again, and similar images, during the scan, and afterwards volunteers completed a memory test in which they were asked to distinguish the images they had seen before and during the scan from a set of completely new images.

Lead researcher Dr Angharad de Cates, who presented the findings the European College of Neuropsychopharmacology conference in Lisbon, said participants who had taken prucalopride for six days performed much better than those receiving placebo on the memory test.

“The prucalopride group identified 81% of previously viewed images versus 76% in the placebo group. Statistical tests indicate that this was a fairly large effect – such an obvious cognitive improvement with the drug was a surprise to us,” she added.

Compared with those taking the placebo, those who took prucalopride were significantly better at the memory test after the scan and their fMRI scans indicated enhanced activity in brain areas related to cognition and memory, such as the hippocampus and the right angular gyrus.

Senior author Dr Susannah Murphy, senior research fellow, said: “Even when the low mood associated with depression is well treated with conventional antidepressants, many patients continue to experience problems with their memory. Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms.”

Further studies are planned to see if prucalopride and other 5HT4 agonists findings can be replicated in patient and clinically vulnerable populations.

De Cates A, Wright L, Martens M et al. Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task. Translational Psychiatry 4 October 2021; doi: 10.1038/s41398-021-01568-4

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