Cholecystokinin is the main hormonal regulator of gallbladder motility.
Dexloxiglumide, the active enantiomer of
loxiglumide, interacts competitively with CCK1 receptors as determined in preclinical studies, such as specific radioligand binding assays or functional studies on isolated guinea pig gallbladder, where it inhibited smooth muscle cell contractions induced by
cholecystokinin-octapeptide (CCK-8), the most prominent active forms of
cholecystokinin.
Dexloxiglumide has a potent antagonistic effect, of a competitive nature, on human gallbladder
cholecystokinin type 1 receptors. In isolated human gallbladder,
dexloxiglumide produced a concentration-dependent rightward shift of the
cholecystokinin-octapeptide curve, without affecting its maximal response. Gallbladder motility was evaluated in clinical studies.
Dexloxiglumide, orally administered to healthy volunteers at putative therapeutic doses, did not interfere with post-prandial gallbladder kinetics, despite an increase of fasting gallbladder volume. At present,
dexloxiglumide is in an advanced stage of clinical research in gastroenterology. Overall, clinical observations suggest that
dexloxiglumide may become an effective treatment in several
gastrointestinal disorders. Moreover, the beneficial effects can be obtained without increasing the risk of
gallstones formation, a potential hazard subsequent to the inhibition of gallbladder contractions and the resulting bile stasis. The potent and selective antagonist
dexloxiglumide may offer a possible therapeutic tool for use not only in
functional gastrointestinal disorders, such as
irritable bowel syndrome,
constipation,
gastroesophageal reflux disease and functional
dyspepsia, but also in other pathologies, such as biliary colics,
pancreatic diseases and gastrointestinal
tumors.