Translational gastrointestinal pharmacology in the 21st century: 'the lesogaberan story'.
The development of the novel γ-aminobutyric acid type-B receptor (GABAB) agonist lesogaberan is presented as an example of a partly successful translational strategy in the field of gastroenterology. Data on transient lower esophageal sphincter relaxations (TLESRs) and gastroesophageal reflux inhibition from preclinical models translated well to clinical studies in healthy volunteers and patients with gastroesophageal reflux disease (GERD). Animal models have also been used successfully to predict the effect of other target mechanisms on TLESRs in humans. However, while translation of physiology to symptomatology in patients with GERD was achieved, the effect size was too small to be of clinical significance. A deeper understanding of the cause of symptoms in different patient categories is therefore required.
Department of Gastroenterology, University Hospital Leuven, Catholic University of Leuven, Belgium.
Guy E
GE
Boeckxstaens
Hans
H
Denison
Jörgen M
JM
Jensen
Anders
A
Lehmann
Magnus
M
Ruth
D000818:Animals; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D004351:Drug Resistance; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000503:physiopathology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D009465:Neuromuscular Agents / Q000494:pharmacology / Q000627:therapeutic use; D010721:Phosphinic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use*; D013045:Species Specificity; D057170:Translational Research, Biomedical
D058786:GABA-B Receptor Agonists; D005765:Gastrointestinal Agents; D009465:Neuromuscular Agents; D010721:Phosphinic Acids; D011437:Propylamines; C545087:lesogaberan; D001418:Baclofen