ketamine + prucalopride

Ketamine + prucalopride is a combination of two small molecule drugs—ketamine, an NMDA receptor antagonist with established anesthetic and antidepressant use, and prucalopride, a selective serotonin 5-HT4 receptor agonist approved for chronic idiopathic constipation. Preclinical research demonstrates that simultaneous administration of ketamine and prucalopride yields additive behavioral and neural benefits in reducing stress-induced pathophysiology, including reductions in fear, behavioral despair, and hyponeophagia in animal models. The mechanism involves targeting both NMDA and 5-HT4 receptors, thereby modulating glutamatergic and serotonergic neural circuits, and converging on the attenuation of aberrant AMPA receptor-mediated synaptic activity in the hippocampus. This combination has not been approved as a marketed product, but has been investigated in preclinical settings for potential use in stress-related psychiatric disorders[1][2][3][4].