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

Abstract

SUMMARY BackgroundTransient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD).

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

“…110, 111 Therefore, more specific, peripherally acting GABA-B agonists are currently being developed that aim to overcome the central side effects. 55,112 A recent study assessed the addition of the more peripherally specific GABA-B agonist lesogaberan to conventional PPI therapy in patients with refractory symptoms and a decrease in reflux events and an increase in LOS pressure was observed. 113 However, some central side effects like headache and paraesthesia may occur when using lesogaberan.…”

“…113 However, some central side effects like headache and paraesthesia may occur when using lesogaberan. 112 Widespread application of GABA-B receptor modulators as add-on therapy in refractory GERD patients is likely to take place when more specific agents with fewer side effects become available.…”

Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia

“…4,5 Preclinical studies in dogs and earlyphase clinical studies in humans showed that lesogaberan decreased the number of TLESRs and episodes of gastroesophageal reflux. [6][7][8] In humans, lesogaberan also increased lower esophageal sphincter pressure. 6,7 However, as many as 50% of the healthy individuals who received lesogaberan during early Phase I clinical trials reported symptoms of paresthesia.…”

Editorial: baclofen and transient lower oesophageal sphincter relaxations – the band plays on ‐ authors' reply

“…Second, it shows that baclofen has multiple beneficial effects on the OGJ, and that the search for well-tolerated and effective GABA-B agonists should continue. [9][10][11] Furthermore, it supports vagal stimulation by the EndoStim â device that suppresses TLOSRs, which may mimic other effects of baclofen at the OGJ without side effects. 12 Finally, the results inform the design of surgical and endoscopic anti-reflux procedures that aim to restore OGJ structure and function to normal.…”