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Constipation drug shows promise for memory enhancement

Journal
Translational Psychiatry
Reuters Health - 06/10/2021 - Prucalopride, a selective serotonin-4 (5-HT4)-receptor agonist primarily used for constipation, may help with memory and thinking, according to new research.

In a small study of healthy young adults, those who took prucalopride for six days performed better on a memory test that than peers taking placebo, with the prucalopride group identifying 81% of previously viewed images versus 76% of the placebo group (P=0.029).

"Statistical tests indicate that this was a fairly large effect - such an obvious cognitive improvement with the drug was a surprise to us," Dr. Angharad de Cates of the University of Oxford, in the U.K., said in a news release.

She presented the study at the European College of Neuropsychopharmacology (ECNP) conference in Lisbon, Portugal, with simultaneous publication in Translational Psychiatry.

Drugs that target the 5-HT4 receptor have shown promise in improving cognitive function in animal studies. In an earlier study, Dr. de Cates and colleagues showed that a single 1-mg dose of prucalopride has pro-cognitive effects across three different tasks of learning and memory (https://bit.ly/3a8N9pF).

To investigate further, they studied 44 adults aged 18 to 36 years; 23 took prucalopride (1-mg daily) and 21 took a placebo.

After six days, all participants had a functional MRI brain scan. Before the scan, they were shown a series of images of animals and landscapes. During the scan, they were shown the same images plus similar images. Following the scan, they took a memory test where they were asked to distinguish the images they had seen before and during the scan from a set of completely new images.

"We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images," the study team reports in their paper.

"At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo," they add.

"Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment," they conclude.

"This is a proof-of-concept study, and so a starting point for further investigation," Dr. de Cates cautioned in the news release.

"We are currently planning and undertaking further studies looking at prucalopride and other 5-HT4 agonists in patient and clinically vulnerable populations, to see if our findings in healthy volunteers can be replicated and have clinical importance," she added.

SOURCE: https://go.nature.com/3la8plo Translational Psychiatry, online October 4, 2021.

By Reuters Staff



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