title: Current developments in pharmacological therapeutics for chronic constipation.
abstract: Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.
authors.affiliation: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chunhuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
keywords: 5-HT, serotonin; 5-HT4 receptor; CC, chronic constipation; CDCA, chenodeoxycholic acid; CFTR, cystic fibrosis transmembrane conductance regulator; CIC, chronic idiopathic constipation; CaCC, calcium-activated chloride channel; Chronic constipation; ClC-2, chloride channel protein 2; ENaC, epithelial sodium channel; GC-C, guanylate cyclase C; GI, gastrointestinal; IBAT, the ileal bile acid transporter (also known as apical sodium-dependent bile acid transporter); IBS-C, irritable bowel syndrome with constipation; IPAN, intrinsic primary afferent neurons; LGP, lubricating gut pill; NHE3, sodium-hydrogen exchanger 3; OIC, opioid-induced constipation; PKGII, protein kinase II; Prokinetic agent; Prosecretory agent; SBMs, spontaneous bowel movements; TGR5, the G-protein-coupled bile acid receptor; hERG, human ether-à-go-go–related gene