Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Inatomi, Nobuhiro; Satoh, Takashi; Satoh, Hiroshi; Ōmura, Satoshi

doi:10.1254/jjp.63.209

Cited by 5 publications

(3 citation statements)

References 17 publications

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“…Similar results in conscious dogs have been demonstrated that low dose motilin (0.2 μg/kg/hr, i. v. infusion) only increased gastric antral motility; more than 5 times higher doses of motilin were required to increase colonic motility in the interdigestive state (Shibata et al, 1995). Inatomi et al (1993) also reported that EM-523, one of the EMA derivatives, administered i. v. infusion at 30 μg/kg/h could induce stronger MMC-like contractions in the gastric antrum, but failed to induce colonic motor activity in conscious dogs. There may be a difference in sensitivity to motilin and motilin receptor agonists between the gastric antrum and the colon in dogs.…”

Section: Discussionsupporting

confidence: 69%

Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs

Ozaki¹,

Sudo²,

Muramatsu³

et al. 2007

Inflammopharmacol

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The prokinetic effects of mitemcinal, an orally active motilin receptor agonist, on the lower gastrointestinal tracts were investigated in conscious dogs. Oral administration of mitemcinal (0.1-1 mg/kg) stimulated colonic motility, which was measured by chronically implanted force-transducers, as well as gastric motility in a dose-dependent manner. The gastrointestinal contractile activities induced by mitemcinal were inhibited by the continuous intravenous infusion of GM-109, a selective motilin receptor antagonist. Oral administration of mitemcinal (0.3-3 mg/kg) also accelerated bowel movement after feeding without inducing diarrhea in dogs. The results demonstrate that mitemcinal stimulates colonic motility via motilin receptors and the effect of mitemcinal on colonic motility may reflect bowel movement after feeding. Thus, mitemcinal could be a promising agent for treatment of not only the upper but also the lower gastrointestinal motility disorders.

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Section: Discussionsupporting

confidence: 69%

Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs

Ozaki¹,

Sudo²,

Muramatsu³

et al. 2007

Inflammopharmacol

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“…An alternative, not exclusive to the direct action of erythromycin, is that the central action of erythromycin is not related to erythromycin itself but to another factor. It has been suggested that the final nervous pathway for erythromycin derivative (EM-523) might involve facilitation of serotoninergic transmission (18,31). A similar regulation has also been demonstrated for motilin (20).…”

Section: Discussionmentioning

confidence: 78%

Erythromycin gastrokinetic activity is partially vagally mediated

Mathis¹,

Malbert²

1998

American Journal of Physiology-Gastrointestinal and Liver Physi

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Erythromycin overcomes postvagotomy gastroparesia in patients without a distal stomach and functional pylorus. We investigate the role of the vagus in gastric emptying increased by erythromycin, using a model that preserves the physiology of the distal stomach and pylorus. The effects of erythromycin lactobionate (10 mg/kg) on transpyloric flow pattern and pyloric resistance were evaluated during repetitive bilateral vagal cooling in anesthetized pigs. Vagal cooling during erythromycin infusion produced a marked decreased of pyloric outflow (23 ± 1.1 vs. 50 ± 2.6 ml/min) related to a reduced stroke volume of the flow pulses (7.8 ± 3.31 vs. 14.1 ± 2.44 ml). The amplitude and frequency of gastric and duodenal pressure events were unchanged or slightly reduced during vagal cooling. The smaller stroke volume of flow pulse was the consequence of increased pyloric resistance (6.2 ± 1.98 vs. 2.3 ± 0.21 mmHg ⋅ ml−1 ⋅ s), which is associated with changes in the temporal relationship between a pyloric pressure event and flow pulse. In conclusion, erythromycin activity on the pylorus requires the integrity of vagal pathways. Enhancement of gastric outflow by erythromycin is also modulated by the vagus, since pyloric resistance was able to overcome increased gastric motility.

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“…It has been previously reported [16][17][18] that injection or infusion of motilin (0.1-1.0 Ìg/kg) induced phase III contractile activity in the gastric antrum. Moreover, we reported earlier [4] that SK-896 and human motilin bind the rabbit gastroduodenal motilin receptor with equal ability and that the 50% inhibitory concentrations for binding of 125 I-motilin to this receptor were 3.5 B 1.5 and 3.1 B 1.8 nmol/l, respectively.…”

Section: Discussionmentioning

confidence: 93%

Gastroprokinetic Effect and Mechanism of SK-896, a New Motilin Analogue, during the Interdigestive Period in Conscious Dogs

Tsukamoto

Tagi²,

Nakazawa³

et al. 2001

Pharmacology

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SK-896 [(Leu¹³)motilin-Hse] is a new human motilin analogue synthesized from Escherichia coli using a biotechnological method. We investigated the gastrointestinal motor-stimulating effect of SK-896 and the mechanism of this effect using implanted force transducers in conscious dogs. Infusion of SK-896 during phase I in the interdigestive state induced interdigestive migrating contractions like motility in the gastroduodenum. The motility index (MI_0–20) of gastric antrum motor activity induced by SK-896 was increased dose dependently (r = 0.830, p < 0.001), and the MI_0–20 induced by SK-896 at a dose of 0.25 µg/kg/h for 20 min was the same as that for spontaneous phase III contractions. The SK-896-induced MI_0–20 was significantly decreased by atropine, hexamethonium, dopamine, granisetron, and yohimbine. Conversely, ketanserin, phentolamine, timolol, and naloxone did not have significant effects on SK-896-induced MI_0–20. The effects of these drugs on human motilin (0.25 µg/ kg/h for 20 min) induced MI_0–20 were the same as those of SK-896. These results indicate that SK-896 induces gastrointestinal motility during the interdigestive period in dogs with regulation of acetylcholine release from the cholinergic nerve terminal via the parasympathetic nervous system in the same fashion as human motilin.

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Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Cited by 5 publications

References 17 publications

Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs

Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs

Erythromycin gastrokinetic activity is partially vagally mediated

Gastroprokinetic Effect and Mechanism of SK-896, a New Motilin Analogue, during the Interdigestive Period in Conscious Dogs

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