A drug currently prescribed to treat chronic constipation may have unintended, beneficial effects – A study has shown the drug improves cognition and memory.
Previous studies conducted on animals have suggest drugs that target the seratonin 5-HT₄ receptor may help to improve cognitive function, although reproducing the results in human subjects in clinical trials has been problematic due to concerns about potential side effects from the medications.
Researchers in the United Kingdom were able to get around these issues by studying the effects of a 5-HT₄ receptor agonist that has been approved for use on patients, which has an acceptable and low risk of side effects when taken under medical supervision.
Prucalopride acts as a selective, high affinity serotonin 5-HT₄ receptor agonist and is used to target the impaired motility associated with chronic constipation to normalize bowel movements. In a clinical trial of the drug to test its effect on cognitive function, 44 healthy individuals aged 18-36 were recruited, 23 of whom were given the drug and 21 were given a placebo.
After 6 days, all individuals underwent an fMRI scan, prior to which each was shown a series of images of animals and landscapes. The images were shown again during the scan along with similar images, and after the scan they underwent a memory test. They were told to identify the images they viewed before and during the fMRI scan from a new set of images.
Individuals who were given prucalopride performed better than the control group and correctly identified 81% of the images they had viewed before and during the scan compared to 76% in the placebo group, which statistically was shown to be a large change, suggesting the drug did result in cognitive improvement. The fMRI scans also showed enhanced activity in the regions of the brain involved in cognition and memory compared to the control group.
“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,” said Dr Susannah Murphy, Senior Research Fellow, University of Oxford and senior author of the study.
The findings of the study were presented at the European College of Neuropsychopharmacology conference in Lisbon and are detailed in the paper – Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task – which was recently published in Nature Translational Psychiatry. DOI: 10.1038/s41398-021-01568-4