Laxative may improve cognitive performance

An explorative study in healthy subjects suggests that an existing drug to treat constipation, prucalopride, has pro-cognitive effects in humans. This drug might be a new approach for the treatment of patients with cognitive impairment secondary to psychiatric disorders, including depression [1,2].

Prucalopride is a selective and specific agonist of the 5-HT₄ serotonin receptor. Serotonin is the neurotransmitter that is targeted by serotonin selective reuptake inhibitor antidepressants. Prucalopride is primarily indicated for symptomatic treatment of chronic constipation in adults. Animal studies suggest that 5-HT₄ receptor agonism enhances cognition, explained Ms Angharad de Cates (University of Oxford, UK) [3]. Concerns about side effects have thus far hindered the study of 5-HT₄ agonists' cognitive effects. In a proof-of-concept study (NCT03572790), 44 healthy volunteers aged 18–36 years were randomised to prucalopride (n=23) or placebo (n=21). On day 6, they underwent a functional MRI brain scan. Before entering the scanner, they were shown a series of images of animals and landscapes. They viewed these again plus similar images during the scan. After the scan, participants performed a memory task: they were asked to distinguish the images they had seen before and during the scan from a set of completely new images.

Prucalopride was associated with improved cognitive performance on the memory task. The prucalopride group identified 81% of previously viewed images versus 76% in the placebo group (P=0.029). “Such an obvious cognitive improvement with the drug was a surprise to us,” noted Ms De Cates. Following memory encoding, 5-HT₄ agonism also increased activation in the hippocampus and in the right angular gyrus. Reduced activation in this region is a known biomarker for cognitive impairment. No significant side effects were reported by any of the participants in this study. Further studies of prucalopride and other 5-HT₄ agonists are underway.

1. 
   
   1. De Cates L, et al. Deja-vu? Can the 5HT4 agonist, prucalopride, improve cognition in humans? IN.08.03, ECNP 2021 Congress, 2–5 October.
   2. De Cates L, et al. Transl Psychiatry. 2021;11(1):497.
   3. Lamirault L, Simon H. Neuropharmacology 2001;41(7):844–53.

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Posted on 26 November 202126 November 2021