Ulimorelin (INN, USAN) (developmental code name TZP-101) is a drug with a modified cyclicpeptidestructure which acts as a selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a).[1] Unlike many related drugs, ulimorelin has little or no effect on growth hormone (GH) release in rats.[2] However, like ghrelin and other ghrelin agonists, ulimorelin does stimulate GH release with concomitant increases in insulin-like growth factor 1 (IGF-1) in humans.[3] It has been researched for enhancing gastrointestinal motility, especially in gastroparesis[4] and in aiding recovery of bowel function following gastrointestinal surgery, where opioidanalgesic drugs used for post-operative pain relief may worsen existing constipation.[5][6][7][8] While ulimorelin has been shown to increase both upper and lower gastrointestinal motility in rats,[8] and showed promising results initially in humans,[4][6] it failed in pivotal clinical trials in post operative ileus.[7]
^Hoveyda HR, Marsault E, Gagnon R, Mathieu AP, Vézina M, Landry A, et al. (December 2011). "Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): Development of ulimorelin (TZP-101) from hit to clinic". Journal of Medicinal Chemistry. 54 (24): 8305–20. doi:10.1021/jm2007062. PMID22106937.
^Lasseter KC, Shaughnessy L, Cummings D, Pezzullo JC, Wargin W, Gagnon R, et al. (February 2008). "Ghrelin agonist (TZP-101): safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study". Journal of Clinical Pharmacology. 48 (2): 193–202. doi:10.1177/0091270007310380. PMID18199894. S2CID206433703.
^ abcWargin W, Thomas H, Clohs L, St-Louis C, Ejskjaer N, Gutierrez M, et al. (2009). "Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study". Clinical Drug Investigation. 29 (6): 409–18. doi:10.2165/00044011-200929060-00004. PMID19432500. S2CID23063963.
^Popescu I, Fleshner PR, Pezzullo JC, Charlton PA, Kosutic G, Senagore AJ (February 2010). "The Ghrelin agonist TZP-101 for management of postoperative ileus after partial colectomy: a randomized, dose-ranging, placebo-controlled clinical trial". Diseases of the Colon and Rectum. 53 (2): 126–34. doi:10.1007/DCR.0b013e3181b54166. PMID20087086. S2CID25357270.
^ abShaw M, Pediconi C, McVey D, Mondou E, Quinn J, Chamblin B, Rousseau F (July 2013). "Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials". Diseases of the Colon and Rectum. 56 (7): 888–97. doi:10.1097/DCR.0b013e31829196d0. PMID23739196. S2CID20364202.
^Fraser GL, Venkova K, Hoveyda HR, Thomas H, Greenwood-Van Meerveld B (February 2009). "Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus". European Journal of Pharmacology. 604 (1–3): 132–7. doi:10.1016/j.ejphar.2008.12.011. PMID19121631.