Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function

Kamerling, Ingrid M C; Haarst, Aernout D. van; Burggraaf, Jacobus; Schoemaker, Rik C.; Kam, Marieke L. de; Heinzerling, Hartmut; Cohen, Adam F.; Masclee, Ad

doi:10.1046/j.1365-2125.2003.02034.x

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…TZP-201 reduced motilin-induced contractions of the colon in S. murinus 228 . In humans, RWJ-68023 antagonized the tonic effect of motilin on the proximal stomach 229 . None of these antagonists have been advanced to large clinical trials, at least in part because of a lack of established end points (patient-reported outcomes) and issues with patient selection and magnitude of therapeutic effect.…”

Section: Motilin Receptor Antagonistsmentioning

confidence: 92%

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Motilin: from gastric motility stimulation to hunger signalling

et al. 2019

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After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution -with the use of knockout models -sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease. Luminal stimuli, such as bitter tastants, have been identified as modulators of motilin release, with effects on hunger and food intake. The current state of knowledge and potential implications for therapy are summarized in this Review.

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Section: Motilin Receptor Antagonistsmentioning

confidence: 92%

“…MA-2029, GM-109, TZP-201 and RWJ-68023 are all motilin receptor antagonists [226][227][228][229] . In dogs, MA-2029 inhibited gastrointestinal motility induced by motilin without affecting gastric emptying 230 .…”

Section: Motilin Receptor Antagonistsmentioning

confidence: 99%

Motilin: from gastric motility stimulation to hunger signalling

et al. 2019

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“…It is unlikely that motilin is released in sufficient amounts during eating to significantly affect gastric motility in healthy volunteers (Boivin et al ., ). This view appears to be consistent with the observation that the motilin receptor antagonist RWJ‐68023 did not affect proximal gastric volume in healthy volunteers (Kamerling et al ., ). However, the latter experiments should be treated with caution because even high doses of RWJ‐68023 only partially prevent the ability of motilin to contract the stomach.…”

Section: Functions Of Endogenous Motilinmentioning

confidence: 97%

Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists

Sanger

Wang

Hobson

et al. 2013

British J Pharmacology

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The gastrointestinal hormone motilin has been known about for >40 years, but after identification of its receptor and subsequent development of new tools and methods, a reappraisal of its actions is required. Firstly, it is important to note that motilin and ghrelin receptors are members of the same family (similar genomic organization, gastrointestinal distribution and abilities to stimulate gastrointestinal motility), yet each fails to recognize the ligand of the other; and whereas ghrelin and ghrelin receptors are widespread outside the gastrointestinal tract, motilin and its receptors are largely restricted to the gastrointestinal tract. Secondly, although some studies suggest motilin has activity in rodents, most do not, and receptor pseudogenes exist in rodents. Thirdly, motilin preferentially operates by facilitating enteric cholinergic activity rather than directly contracting the muscle, despite the relatively high expression of receptor immunoreactivity in muscle. This activity is ligand-dependent, with short-lasting actions of motilin contrasting with longer-lasting actions of the non-selective and selective motilin receptor agonists erythromycin and GSK962040. Finally, the use of erythromycin (also an antibiotic drug) to treat patients requiring acceleration of gastric emptying has led to concerns over safety and potential exacerbation of antibiotic resistance. Replacement motilin receptor agonists derived from erythromycin (motilides) have been unsuccessful. New, non-motilide, small molecule receptor agonists, designed to minimize self-desensitization, are now entering clinical trials for treating patients undergoing enteral feeding or with diabetic gastroparesis. Thus, for the translational pharmacologist, the study of motilin illustrates the need to avoid overreliance on artificial systems, on structural information and on animal studies. LINKED ARTICLESThis article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx

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“…Motilin, a 22-amino-acid polypeptide, is related to the regulation of gastrointestinal motility (Itoh, 1997) and new chemical entities which act on motilin receptors have recently been expected for the treatment of functional gastrointestinal tract disorders (McCallum and Cynshi, 2007;Kamerling et al, 2004). Irritable bowel syndrome (IBS) is a functional bowel disorder in which abdominal discomfort or pain is associated with altered bowel habits (Thompson et al, 1999).…”

Section: Introductionmentioning

confidence: 99%