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Alimentary pharmacology & therapeutics

The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease.


PMID 11552906

Abstract

Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role. To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide. 10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years). Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order. During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)]. Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.

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SML0130
Loxiglumide, ≥97% (HPLC)
C21H30Cl2N2O5