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Ghrelin Receptor Agonist (ghrelin + receptor_agonist)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009
N. EJSKJAER
Summary Background, TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis. Aim, To assess safety and effects of TZP-101 in diabetes patients with symptomatic gastroparesis. Methods, Adults with type 1 or type 2 diabetes mellitus received placebo and TZP-101 (80, 160, 320 or 600 ,g/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses. Results, Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and ,29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP-101 infusion were not statistically significant. Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between TZP-101 and placebo. Conclusions, This proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying. [source]

Ghrelin receptor agonists: a new class of prokinetic agents

NEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2010
Article first published online: 17 JUN 2010
No abstract is available for this article. [source]

Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecation

NEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2009
A. D. Shafton
Abstract, Agonists of ghrelin receptors that cross the blood,brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo-sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood,brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1,10 nmol L,1, but was >1000-fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood ratio at steady state was 0.7 : 1. GSK894281 administered orally (1,100 mg kg,1) caused a prompt, dose-related production of faecal pellets; at 10 mg kg,1 faecal output was four times greater than after carrier. The output was the greatest in the first half hour and subsided over the next 90 min. At an oral dose of 10 mg kg,1, the compound was effective on eight successive days. Faecal output was, on average, increased threefold over control in the 2 h after administration on each of the 8 days. This dose also significantly increased food consumption. Rats showed no adverse behavioural effects to the drug on a single application, but at the end of a week of administration they avoided the gavaging pipette. Oral administration of ghrelin receptor agonists that enter the central nervous system could possibly be used to relieve acute cases of constipation or to clear the bowel for colonoscopy. [source]