Cisapride (monohydrate)

Cisapride (R 51619) monohydrate is an orally active, selective 5-HT₄ receptor agonist with an EC₅₀ of 140 nM. Cisapride monohydrate also acts as an hERG potassium channel blocker with an IC₅₀ of 9.4 nM. Cisapride monohydrate exerts gastrointestinal prokinetic effects by activating 5-HT₄ receptors, but it also blocks the hERG potassium channel responsible for the repolarization phase of cardiac action potentials, delaying repolarization and thus prolonging the action potential duration. Cisapride monohydrate can be used in research related to gastrointestinal dysfunction, gastroesophageal reflux disease, functional dyspepsia, chronic gastritis, gastroparesis, ulcerative colitis and necrotizing enterocolitis^{[1][2][3][4][5]}. In Vitro:Cisapride (R 51619) (0.3-30 μM; 500 ms) monohydrate inhibits Kv4.3 potassium channels stably expressed in Chinese hamster ovary cells in a concentration-dependent manner, with an IC₅₀ of 9.8 μM, and accelerates current decay^[3].
Cisapride (10 min) monohydrate potently inhibits hERG potassium currents in HEK293 cells stably expressing hERG channels, with an IC₅₀ of 9.4 nM^[5]. In Vivo:Cisapride (R 51619) monohydrate (1 mM; i.p.; single dose) exhibits activities of increasing heart rate and left ventricular ejection fraction in anesthetized transgenic mouse animal models^[2].
Cisapride monohydrate improves intestinal motor function, significantly reduces TNF-α expression in the intestinal mucosa, and alleviates the severity of necrotizing enterocolitis in a mouse model of necrotizing enterocolitis^[1].
Cisapride (2-4 mg/kg; once daily; i.p. or p.o.; consecutive dosing for 6 days) monohydrate does not alter the severity of colonic injury in TNBS-induced colitis in male Wistar rats^[4].