Prucalopride

Prucalopride is a potent and selective agonist of the serotonin (5-HT) receptor subtype 5-HT4 (Kis = 2.5 and 8 nM for human 5-HT4A and 5-HT4B, respectively). 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 (sigma1) receptors and mouse 5-HT3 receptors (Kis = 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-HT2A and 5-HT3 antagonists ketanserin (Cay-22058) and granisetron (Cay-21239), respectively. 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. Formulations containing prucalopride have been used in the treatment of chronic idiopathic constipation.Formal Name: 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide. CAS Number: 179474-81-8. Molecular Formula: C18H26ClN3O3. Formula Weight: 367.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMF:PBS (pH 7.2) (1:9): 0.1 mg/ml, DMSO: 10 mg/ml, Ethanol: 10 mg/ml. lambdamax: 225, 276, 300 nm. SMILES: NC1=C(CCO2)C2=C(C(NC3CCN(CCCOC)CC3)=O)C=C1Cl. InChi Code: InChI=1S/C18H26ClN3O3/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14/h11-12H,2-10,20H2,1H3,(H,21,23). InChi Key: ZPMNHBXQOOVQJL-UHFFFAOYSA-N.