Oral erythromycin and symptomatic relief of gastroparesis a systematic review

Maganti, Kalyani

doi:10.1016/s0002-9270(02)05835-5

Cited by 42 publications

(55 citation statements)

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“…No studies evaluating the utility of metoclopramide in gastroparetic patients have been published in the last 5 years. Erythromycin is a potent gastrokinetic [111][112][113][114][115] , although its effi cacy in relieving symptoms has not been clearly demonstrated [116] . GM-611, a motilin agonist, is under development.…”

Section: Gastroparesismentioning

confidence: 99%

Gastrointestinal Motility Disorders: An Update

Lacy

Weiser

2006

Dig Dis

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Gastrointestinal motility disorders encompass a wide array of signs and symptoms that can occur anywhere throughout the luminal gastrointestinal tract. Motility disorders are often chronic in nature and dramatically affect patients’ quality of life. These prevalent disorders cause a tremendous impact both to the individual patient and to society as a whole. Significant progress has been made over the last 5 years in understanding the etiology and pathophysiology of gastrointestinal motility disorders. This clinical update will focus on seven of the most common gastrointestinal motility disorders (achalasia, non-achalasia esophageal motility disorders, dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome, and chronic constipation) with an emphasis on current treatment options and new therapeutic modalities.

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Section: Gastroparesismentioning

confidence: 99%

Gastrointestinal Motility Disorders: An Update

Lacy

Weiser

2006

Dig Dis

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“…1,2 Treatment with prokinetic agents, including cisapride, domperidone, metoclopramide and erythromycin, forms the mainstay of therapy of symptomatic diabetic gastroparesis. [3][4][5][6][7][8][9][10] Short-term administration of all of these drugs has been shown to accelerate gastric emptying, although there is only a poor correlation between the magnitude of symptomatic improvement and the change in gastric emptying. [2][3][4] All of the currently available drugs have significant limitations.…”

Section: Introductionmentioning

confidence: 99%

Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis

Russo

Stevens

Giles

et al. 2004

Aliment Pharmacol Ther

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SUMMARYBackground: KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans. Aim: To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis. Methods: Twenty-nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and 'meal-related' symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days.

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“…Motilin receptor represents an attractive drug target for the treatment of functional gastrointestinal disorders (Chovet, 2000;Camilleri, 2002;Sanger and Hicks, 2002;Maganti et al, 2003). However, the clinical utility of long-term MR agonist administration has been limited by the lack of efficacy after prolonged exposure, as demonstrated by ABT-229 (Talley et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…However, the clinical utility of long-term MR agonist administration has been limited by the lack of efficacy after prolonged exposure, as demonstrated by ABT-229 (Talley et al, 2000). It is possible that MR tachyphylaxis was the primary cause for lack of efficacy, although gastroparesis clinical trials have been criticized for their small sample sizes, uncontrolled designs, short duration, and inadequate symptom assessment (Tack and Peeters, 2001;Camilleri, 2002;Maganti et al, 2003). Clinical data show that a single dose of ABT-229 strongly increased gastric emptying after the first meal in healthy volunteers, but no effect was observed after the second meal despite the presence of considerable residual drug concentrations in the serum (Verhagen et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Agonist-Induced Motilin Receptor Trafficking and Its Implications for Tachyphylaxis

Lamian

Rich

et al. 2005

Mol Pharmacol

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The motilin receptor (MR) is a member of the seven-transmembrane receptor family and is expressed throughout the gastrointestinal tract of humans and other species. Motilin, the natural MR peptide ligand, has profound stimulatory effects on gastrointestinal contractility, indicating a therapeutic potential for MR modulators. However, long-term clinical use of certain MR agonists is limited by tachyphylaxis, a reduced responsiveness to repeated compound exposure. This study was meant to characterize the ligand-induced endocytosis of MR and to test whether receptor trafficking contributes to tachyphylaxis. A cell-based assay was developed by fusing a green fluorescent protein (GFP) moiety to the motilin receptor, and high-content biology instrumentation was used to quantify time and dose dependence of MR-GFP endocytosis. Maximal internalization of MR-GFP was induced after 45 min of constant exposure to 80 nM motilin. This process was disrupted by nocodazole, suggesting an essential role for microtubules. Internalized MR-GFP vesicles disappeared within 15 to 45 min of motilin withdrawal but did not overlap with the lysosomal compartment, indicating that MR-GFP escaped degradation and was recycled back to the plasma membrane. It is noteworthy that the kinetics of MR-GFP redistribution varied substantially when stimulated with motilin, erythromycin, 6,9-hemiacetal 8,9-anhydro-4Љ-deoxy

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Oral erythromycin and symptomatic relief of gastroparesis a systematic review

Cited by 42 publications

References 0 publications

Gastrointestinal Motility Disorders: An Update

Gastrointestinal Motility Disorders: An Update

Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis

Characterization of Agonist-Induced Motilin Receptor Trafficking and Its Implications for Tachyphylaxis

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