Effect of lesogaberan, a novel GABAB-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects

Alimentary Pharmacology and Therapeutics

Volumn 31, Issue 11, 2010, Pages 1208-1217

  Boeckxstaens, G E ^a,b   Rydholm, H ^c   Lei, A ^a   Adler, J ^c   Ruth, M ^c  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; AZD 3355; BACLOFEN; LESOGABERAN; PLACEBO; UNCLASSIFIED DRUG;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; AREA UNDER THE CURVE; ARTICLE; BURNING SENSATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIZZINESS; DRUG ABSORPTION; DRUG ACTIVITY; DRUG EFFECT; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; ESOPHAGUS MANOMETRY; FATIGUE; GASTROINTESTINAL DISEASE; HEAT SENSATION; HUMAN; HUMAN EXPERIMENT; LOW DRUG DOSE; LOWER ESOPHAGUS SPHINCTER; MALE; MAXIMUM PLASMA CONCENTRATION; NEUROLOGIC DISEASE; NORMAL HUMAN; PARESTHESIA; PH MEASUREMENT; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; SMOOTH MUSCLE RELAXATION; SOMNOLENCE; TIME TO MAXIMUM PLASMA CONCENTRATION; URINE VOLUME;

ADOLESCENT; ADULT; BACLOFEN; CROSS-OVER STUDIES; ESOPHAGEAL SPHINCTER, LOWER; GABA AGONISTS; GASTROESOPHAGEAL REFLUX; HUMANS; MALE; MANOMETRY; MIDDLE AGED; MUSCLE RELAXATION; PHOSPHINIC ACIDS; PROPYLAMINES; YOUNG ADULT;

EID: 77951811841     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/j.1365-2036.2010.04283.x     Document Type: Article

References (34)

1. Armstrong D. Systematic review: persistence and severity in gastroesophageal reflux disease. Aliment Pharmacol Ther 2008 28 : 841 853.
2. Wiklund I, Talley NJ. Update on health-related quality of life in patients with gastroesophageal reflux disease. Expert Rev Pharmacoeconomics Outcomes Res 2003 3 : 341 350.
3. Vakil N, Veldhuyzen van Zanten S, Kahrilas P, et al. The Montreal definition and classification of gastro-esophageal reflux disease (GERD) - a global evidence-based consensus. Am J Gastroenterol 2006 101 : 1900 1920.
4. Bredenoord AJ, Weusten BL, Curvers WL, et al. Determinants of perception of heartburn and regurgitation. Gut 2006 55 : 313 318.
5. 2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2004 : CD002095.
6. Donnellan C, Sharma N, Preston C, et al. Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. Cochrane Database Syst Rev 2005 4 : CD003245.
7. Armstrong D, Pare P, Pericak D, et al. Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease. Am J Gastroenterol 2001 96 : 2849 2857.
8. Hatlebakk JG, Hyggen A, Madsen PH, et al. Heartburn treatment in primary care: randomised, double blind study for 8 weeks. BMJ 1999 319 : 550 553.
9. Meineche-Schmidt V, Hauschildt Juhl H, Ostergaard JE, et al. Costs and efficacy of three different esomeprazole treatment strategies for long-term management of gastro-oesophageal reflux symptoms in primary care. Aliment Pharmacol Ther 2004 19 : 907 915.
10. Fass R. Proton-pump inhibitor therapy in patients with gastro-oesophageal reflux disease: putative mechanisms of failure. Drugs 2007 67 : 1521 1530.
11. Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut 2006 55 : 1398 1402.
12. Vela MF, Camacho-Lobato L, Srinivasan R, et al. Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology 2001 120 : 1599 1606.
13. Dent J, Dodds WJ, Friedman RH, et al. Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects. J Clin Invest 1980 65 : 256 267.
14. Dodds WJ, Dent J, Hogan WJ, et al. Mechanisms of gastroesophageal reflux in patients with reflux esophagitis. N Engl J Med 1982 307 : 1547 1552.
15. Smid SD, Young RL, Cooper NJ, et al. GABA(B)R expressed on vagal afferent neurones inhibit gastric mechanosensitivity in ferret proximal stomach. Am J Physiol Gastrointest Liver Physiol 2001 281 : G1494 501.
16. McDermott CM, Abrahams TP, Partosoedarso E, et al. Site of action of GABA(B) receptor for vagal motor control of the lower esophageal sphincter in ferrets and rats. Gastroenterology 2001 120 : 1749 1762.
17. Lidums I, Lehmann A, Checklin H, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology 2000 118 : 7 13.
18. Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut 2002 50 : 19 24.
19. Vela MF, Tutuian R, Katz PO, et al. Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH. Aliment Pharmacol Ther 2003 17 : 243 251.
20. Koek GH, Sifrim D, Lerut T, et al. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut 2003 52 : 1397 1402.
21. Lehmann A, Brändén L, Carlsson A, et al. AZD3355, a novel GABA(B) receptor agonist, inhibits transient lower esophageal sphincter relaxations in the dog [abstract]. Gastroenterology 2008 134 (4 Suppl 1 A49.
22. Brändén L, Carlsson A, Jensen J, et al. The novel GABA(B) receptor agonist AZD3355 inhibits acid reflux and reduces esophageal acid exposure as measured by 24h pHmetry in dogs [abstract]. Gastroenterology 2008 134 (4 Suppl 1 A715.
23. Lehmann A, Blackshaw LA, Elebring T, et al. The new reflux inhibitor AZD3355 has a low propensity for inducing central side effects due to its affinity for the GABA carrier [abstract]. Gastroenterology 2008 134 (4 Suppl 1 A715.
24. Holloway RH, Penagini R, Ireland AC. Criteria for objective definition of transient lower esophageal sphincter relaxation. Am J Physiol 1995 268 : G128 33.
25. Hirsch DP, Tytgat GN, Boeckxstaens GE. Transient lower oesophageal sphincter relaxations - a pharmacological target for gastro-oesophageal reflux disease? Aliment Pharmacol Ther 2002 16 : 17 26.
26. Lehmann A. Novel treatments of GERD: focus on the lower esophageal sphincter. Eur Rev Med Pharmacol Sci 2008 12 : 103 110.
27. Dent J. Pathogenesis of gastro-oesophageal reflux disease and novel options for its therapy. Neurogastroenterol Motil 2008 20 (Suppl 1 91 102.
28. B receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study. Aliment Pharmacol Ther 2009 30 : 937 946.
29. Lehmann A, Bremner-Danielsen M, Brändén L, et al. Inhibitory effects of GABA(B) receptor agonists on swallowing in the dog. Eur J Pharmacol 2002 448 : 67 70.
30. Boeckxstaens GE, Denison H, Ruth M, et al. Effect of AZD3355, a novel GABA(B) agonist, on reflux and lower esophageal sphincter function in patients with GERD with symptoms despite proton pump inhibitor treatment [abstract]. Gastroenterol 2009 136 (Suppl 1 M1861.
31. Boeckxstaens GE, Beaumont H, Hatlebakk JG, et al. Efficacy and tolerability of the novel reflux inhibitor, AZD3355, as add-on treatment in GERD patients with symptoms despite proton pump inhibitor therapy [abstract]. Gastroenterol 2009 136 (Suppl 1 M1875.
32. Mogyoros I, Bostock H, Burke D. Mechanisms of paresthesias arising from healthy axons. Muscle Nerve 2000 23 : 310 320.
33. Brown DA, Adams PR, Higgins AJ, et al. Distribution of GABA-receptors and GABA-carriers in the mammalian nervous system. J Physiol (Paris) 1979 75 : 667 671.
34. B) receptor agonists as gastroesophageal reflux inhibitors. J Med Chem 2008 51 : 4315 4320.