Prucalopride

Prucalopride is a potent and selective agonist of the serotonin (5-HT) receptor subtype 5-HT₄ (K_is = 2.5 and 8 nM for human 5-HT_4A and 5-HT_4B, respectively).¹ Prucalopride is greater than 250-fold selective for 5-HT₄ over a panel of 53 overexpressed receptors, including 5-HT subtypes, but does bind to human dopamine D₄ and sigma-1 (σ₁) receptors and mouse 5-HT₃ receptors (K_is = 2.3, 3.7, and 3.8 μM, respectively). It induces contractions in guinea pig colon with an EC₅₀ value of 33 nM, an effect that is blocked by the 5-HT₄ antagonist GR113808 but not the 5-HT_2A and 5-HT₃ antagonists ketanserin (Item No. 22058) and granisetron (Item No. 21239), respectively.² It also facilitates non-cholinergic contractions induced by electrical stimulation. In fasted dogs, oral administration of prucalopride increases colonic motility by inhibiting distal colon contractions (ED₅₀ = 0.04 mg/kg), an effect that is blocked by pretreatment with the 5-HT₄ antagonist GR125487. Prucalopride (5-10 mg/kg, s.c.) increases acetylcholine and histamine levels in the rat prefrontal cortex by 2.4-fold and 3-fold, respectively, and increases the power of hippocampal theta oscillations.³ Formulations containing prucalopride have been used in the treatment of chronic idiopathic constipation.

WARNING This product is not for human or veterinary use.

1. Briejer, M.R., Bosmans, J.P., Van Daele, P., et al. The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound. Eur. J. Pharmacol. 423(1), 71-83 (2001).

2. Briejer, M.R., Prins, N.H., and Schuurkes, J.A. Effects of the enterokinetic prucalopride (R093877) on colonic motility in fasted dogs. Neurogastroenterol. Motil. 13(5), 465-472 (2001).

3. Johnson, D.E., Drummond, E., Grimwood, S., et al. The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations. J. Pharmacol. Exp. Ther. 341(3), 681-691 (2012).