Tags

Type your tag names separated by a space and hit enter

The GABA(B) receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study.
Aliment Pharmacol Ther. 2009 Nov 01; 30(9):937-46.AP

Abstract

BACKGROUND

Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required.

AIM

To study the effect of AZD9343, a new selective GABA(B) receptor agonist, in healthy volunteers.

METHODS

A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days.

RESULTS

Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate.

CONCLUSIONS

Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABA(B) agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted.

Authors+Show Affiliations

Academic Medical Centre, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19650825

Citation

Beaumont, H, et al. "The GABA(B) Receptor Agonist AZD9343 Inhibits Transient Lower Oesophageal Sphincter Relaxations and Acid Reflux in Healthy Volunteers: a Phase I Study." Alimentary Pharmacology & Therapeutics, vol. 30, no. 9, 2009, pp. 937-46.
Beaumont H, Smout A, Aanen M, et al. The GABA(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(9):937-46.
Beaumont, H., Smout, A., Aanen, M., Rydholm, H., Lei, A., Lehmann, A., Ruth, M., & Boeckxstaens, G. (2009). The GABA(B) receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study. Alimentary Pharmacology & Therapeutics, 30(9), 937-46. https://doi.org/10.1111/j.1365-2036.2009.04107.x
Beaumont H, et al. The GABA(B) Receptor Agonist AZD9343 Inhibits Transient Lower Oesophageal Sphincter Relaxations and Acid Reflux in Healthy Volunteers: a Phase I Study. Aliment Pharmacol Ther. 2009 Nov 1;30(9):937-46. PubMed PMID: 19650825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The GABA(B) receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study. AU - Beaumont,H, AU - Smout,A, AU - Aanen,M, AU - Rydholm,H, AU - Lei,A, AU - Lehmann,A, AU - Ruth,M, AU - Boeckxstaens,G, Y1 - 2009/07/24/ PY - 2009/8/5/entrez PY - 2009/8/5/pubmed PY - 2010/2/27/medline SP - 937 EP - 46 JF - Alimentary pharmacology & therapeutics JO - Aliment Pharmacol Ther VL - 30 IS - 9 N2 - BACKGROUND: Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. AIM: To study the effect of AZD9343, a new selective GABA(B) receptor agonist, in healthy volunteers. METHODS: A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. RESULTS: Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. CONCLUSIONS: Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABA(B) agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted. SN - 1365-2036 UR - https://www.unboundmedicine.com/medline/citation/19650825/The_GABA_B__receptor_agonist_AZD9343_inhibits_transient_lower_oesophageal_sphincter_relaxations_and_acid_reflux_in_healthy_volunteers:_a_phase_I_study_ L2 - https://doi.org/10.1111/j.1365-2036.2009.04107.x DB - PRIME DP - Unbound Medicine ER -