PF-04995274

PF-04995274 is an orally administered, brain-penetrant small molecule that acts as a partial agonist at the serotonin 4 receptor (5-HT4). It was developed by Pfizer for potential use in cognitive disorders associated with Alzheimer's disease and as a novel antidepressant. The drug exhibits high affinity and selectivity for multiple human 5-HT4 receptor isoforms, with EC50 values in the sub-nanomolar range. Preclinical studies suggested cognitive-enhancing effects, while clinical trials have investigated its impact on cognition and emotional processing in both unmedicated and treatment-resistant patients with major depressive disorder (MDD). Despite initial promise, development for Alzheimer's disease was discontinued by Pfizer around 2011. More recent academic-led trials have explored its short-term effects on cognition and emotional processing in depression[1][2][3][4][5][6][7][9].