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6.30.5.1.4 Motilin receptor agonists

Before recognition of its ability to increase GI motility, the antibiotic erythromycin was widely known for provoking intestinal side effects in patients receiving treatment for infections. In healthy human volunteers, erythromycin dose-dependently increased the gastric emptying of liquids.71 The utility of erythromycin in the treatment of gastroparesis and pseudo-obstruction has been studied, but limitations in study design make conclusions difficult to draw. The search for clinically useful motilin receptor agonist prokinetics initially focused on the erythromycin analogs, EM-523 (25) and EM-574 (26), that stimulate gastric motility and gastric emptying in dogs.72'73 EM-574 is a potent stimulant of gastric emptying in healthy human volunteers.74 The clinical development of motilin receptor agonists has so far been unsuccessful, with ABT-229 (27), a synthetic macrolide devoid of antibiotic properties, being the most studied. ABT-229 has a powerful effect on gastric emptying in the dog, shortening the lag phase and increasing the rate of emptying of a solid meal.75 The effect on motility in the human upper gut is controversial, with some studies showing an effect to increase gastric emptying, and others no effect. ABT-229 has been studied in diabetic gastroparesis and functional dyspepsia where it failed to improve symptoms, and in GERD patients where ABT-229 actually worsened reflux symptoms.78-80 Attempts to reconcile these data have focused on the agonist-specific tachyphylaxis that is seen in this receptor system, with rapid desensitization occurring with many motilin receptor agonists. ABT-229 appears to be particularly active in this regard. In diabetic gastroparesis, another motilin agonist, KC-11458 (28), failed to increase the gastric emptying of either solids or liquids.81 Another motilin receptor agonist, mitemcinal (29, GM-611) has useful prokinetic properties. In patients with diabetic or idiopathic gastroparesis, mitemcinal has been shown to enhance delayed gastric emptying.

Herbal Remedies For Acid Reflux

Herbal Remedies For Acid Reflux

Gastroesophageal reflux disease is the medical term for what we know as acid reflux. Acid reflux occurs when the stomach releases its liquid back into the esophagus, causing inflammation and damage to the esophageal lining. The regurgitated acid most often consists of a few compoundsbr acid, bile, and pepsin.

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