The effects of camicinal, a novel motilin agonist, on gastro‐esophageal function in healthy humans—a randomized placebo controlled trial

Hobson, Ruth M.; Farmer, Adam D.; Dewit, Odile; O’Donnell, Matthew; Hacquoil, Kimberley; Robertson, Darren; Barton, Matthew E.; Dukes, George E.

doi:10.1111/nmo.12663

Cited by 22 publications

(12 citation statements)

References 31 publications

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“…The effects observed with 150 mg camicinal in the present study are very similar to those thought to reflect activation of neural motilin receptors with erythromycin. The current finding that camicinal does not alter esophageal acid exposure is in agreement with previous data reported by Hobson et al . Our finding that camicinal does not alter intestinal motility patterns is in agreement with its lack of small bowel transit time as measured with the wireless motility capsule …”

Section: Discussionsupporting

confidence: 94%

“…On the other hand, although the sample size was small, the findings of the present study confirm that camicinal has the expected effects of this class of agent on interdigestive motility in healthy humans by inducing gastric phase III contractions. In previous studies in healthy subjects, significant stimulation of gastric emptying rates was observed with a camicinal dose of 25 mg or higher …”

Section: Discussionmentioning

confidence: 86%

“…Furthermore, administration of 50 mg camicinal increased gastric emptying and subsequently glucose absorption in feed‐intolerant critically ill patients . Despite its stimulating effect on gastric emptying in humans, camicinal has no effect on esophageal function, small bowel, colonic, or whole gut transit times . So far, the effect of camicinal on interdigestive motility in humans has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…31 Despite its stimulating effect on gastric emptying in humans, camicinal has no effect on esophageal function, small bowel, colonic, or whole gut transit times. 32 So far, the effect of camicinal on interdigestive motility in humans has not been evaluated. The present report describes the influence of different doses of the motilin receptor agonist camicinal on interdigestive gastrointestinal motility in man.…”

mentioning

confidence: 99%

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Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans

Deloose

Depoortere

Hoon

et al. 2017

Neurogastroenterology Motil

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans

Deloose

Depoortere

Hoon

et al. 2017

Neurogastroenterology Motil

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“…Another 5-HT 4 agonist velusetrag also stimulates gastric emptying in healthy volunteers and patients with constipation; trials in gastroparesis are ongoing (85). Camicinal is a novel non-macrolide motilin agonist without antimicrobial activity that promotes solid food emptying in healthy volunteers and patients with type 1 diabetes and symptoms of gastroparesis (86, 87, 88). Preliminary unpublished phase 2 data observed symptom improvements in a trial in diabetic gastroparesis (89).…”

Section: Medications Used To Treat Nausea and Vomitingmentioning

confidence: 99%

Newest Drugs for Chronic Unexplained Nausea and Vomiting

Hasler

2016

Curr Treat Options Gastro

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OPINION STATEMENT Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic assessments (including upper endoscopy) and measures of upper gut function (e.g. gastric emptying testing). Nausea and vomiting in this condition are postulated to result from aberrant peripheral or central neurohumoral activity. A substantial subset of patients satisfies this diagnosis as more than half of individuals referred for scintigraphic testing exhibit normal gastric emptying rates. No randomized, placebo-controlled trials of any medication treatment have been performed in CUNV. However, agents with potential therapeutic benefit in CUNV include antiemetic drugs, neuromodulatory treatments which are proposed to act by reducing gastric sensitivity, and medications with prokinetic action to stimulate upper gut propulsion. Recently approved drugs with antiemetic capability include serotonin antagonists with novel modes of delivery and neurokinin antagonists with or without additional serotonergic blocking capabilities. Existing neuroleptics and pain modifying neuromodulatory therapies with fortuitous antiemetic benefits are being considered for their benefits in this disorder. Furthermore, current investigations will define potential therapeutic actions of agents that stimulate gastric emptying via action on gastroduodenal serotonin, motilin, and ghrelin receptors. This current research may broaden the treatment options for refractory cases of unexplained nausea and vomiting.

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Ghrelin and Motilin Control Systems in GI Physiology and Therapeutics

Sanger

Broad

Callaghan

et al. 2016

Handbook of Experimental Pharmacology

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Ghrelin and motilin are released from gastrointestinal endocrine cells during hunger, to act through G protein-coupled receptors that have closely related amino acid sequences. The actions of ghrelin are more complex than motilin because ghrelin also exists outside the GI tract, it is processed to des-acyl ghrelin which has activity, ghrelin can exist in truncated forms and retain activity, the ghrelin receptor can have constitutive activity and is subject to biased agonism and finally additional ghrelin-like and des-acyl ghrelin receptors are proposed. Both ghrelin and motilin can stimulate gastric emptying, acting via different pathways, perhaps influenced by biased agonism at the receptors, but research is revealing additional pathways of activity. For example, it is becoming apparent that reduction of nausea may be a key therapeutic target for ghrelin receptor agonists and perhaps for compounds that modulate the constitutive activity of the ghrelin receptor. Reduction of nausea may be the mechanism through which gastroparesis symptoms are reduced. Intriguingly, a potential ability of motilin to influence nausea is also becoming apparent. Ghrelin interacts with digestive function through its effects on appetite, and ghrelin antagonists may have a place in treating Prader-Willi syndrome. Unlike motilin, ghrelin receptor agonists also have the potential to treat constipation by acting at the lumbosacral defecation centres. In conclusion, agonists of both ghrelin and motilin receptors hold potential as treatments for specific subsets of digestive system disorders.

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The effects of camicinal, a novel motilin agonist, on gastro‐esophageal function in healthy humans—a randomized placebo controlled trial

Abstract: Camicinal decreases GET and was generally well-tolerated. In health, the direct effects of camicinal are on accelerating GET with a potential secondary benefit of reducing reflux events, which warrant further exploration in patient cohorts.

Cited by 22 publications

References 31 publications

Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans

Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans

Newest Drugs for Chronic Unexplained Nausea and Vomiting

Ghrelin and Motilin Control Systems in GI Physiology and Therapeutics

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