Effects of SK-951, a Benzofuran Derivative, as a Prokinetic Agent in Rats and Dogs.

Takeda, Motohiro; Tsukamoto, Katsura; Yamano, Masaya; Uesaka, Hiroshi

doi:10.1254/jjp.81.292

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…It is well known that the vagus nerve is the most important nerve for the regulation of gastrointestinal motility and it has been reported that although MMC cycles still occur in the interdigestive state in conscious dogs after truncal vagotomy, gastric contractions are greatly suppressed 25 . It has also been reported that vagotomy causes delayed gastric emptying in dogs 26,27 …”

Section: Discussionmentioning

confidence: 99%

Oral Mitemcinal (Gm‐611), an Erythromycin‐derived Prokinetic, Accelerates Normal and Experimentally Delayed Gastric Emptying in Conscious Dogs

Onoma¹,

Kamei

Akima

et al. 2007

Clin Exp Pharma Physio

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1. We examined effects of orally administered mitemcinal, an erythromycin-derived motilin agonist, on gastric emptying and antroduodenal motility in conscious normal dogs and conscious dogs with experimentally delayed gastric emptying. For comparison, we also examined the effects of orally administered cisapride. 2. Gastric emptying was assessed by adding paracetamol to the test meal and determining three of its pharmacokinetic parameters as indices of gastric emptying. Antroduodenal motility was assessed from the output of force transducers chronically implanted in the gastric antrum and duodenum. 3. In normal dogs, mitemcinal (0.25, 0.5 and 1 mg/kg) dose-dependently accelerated gastric emptying, significantly increasing all three indices at doses of 0.5 and 1 mg/kg; cisapride (1, 3 and 10 mg/kg) had no significant effect. Mitemcinal also dose-dependently stimulated antroduodenal motility in the interdigestive and digestive states. Cisapride, at 100-fold the dose, produced similar effects in the interdigestive state, but mixed results in the digestive state. 4. In dogs with delayed gastric emptying induced by subcutaneous clonidine (0.03 mg/kg), mitemcinal (0.25, 0.5 and 1 mg/kg) dose-dependently improved delayed gastric emptying, significantly increasing two of three indices at a dose of 1 mg/kg. Cisapride (1, 3 and 10 mg/kg) caused non-significant increases in the indices of gastric emptying, with roughly bell-shaped dose-response curves. The highest dose of mitemcinal (1 mg/kg) also stimulated antroduodenal motility. 5. In dogs with delayed gastric emptying induced by vagotomy, mitemcinal (0.125, 0.25 and 0.5 mg/kg) dose-dependently improved delayed gastric emptying, significantly increasing all three indices at doses of 0.25 and 0.5 mg/kg. Cisapride (3 mg/kg) restored the indices to roughly prevagotomy levels, but none of the increases was significant. Mitemcinal, at a dose of 0.25 mg/kg, also stimulated antroduodenal motility. 6. Because delayed gastric emptying is the basic characteristic of gastroparesis, the fact that mitemcinal accelerated gastric emptying in dogs with normal and delayed gastric emptying much more robustly than cisapride adds to the evidence that mitemcinal is likely to be useful for the treatment of patients with gastroparesis.

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Section: Discussionmentioning

confidence: 99%

Oral Mitemcinal (Gm‐611), an Erythromycin‐derived Prokinetic, Accelerates Normal and Experimentally Delayed Gastric Emptying in Conscious Dogs

Onoma¹,

Kamei

Akima

et al. 2007

Clin Exp Pharma Physio

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“…The experiment was conducted according to the method reported by Takeda et al (8). To delay gastric emptying, 10 mg / kg of L-NNA was orally administered to rats 24 h before the evaluation of gastric emptying.…”

Section: Evaluation Of Gastric Emptyingmentioning

confidence: 99%

Effects of Rikkunshi-to, a Traditional Japanese Medicine, on the Delay of Gastric Emptying Induced by NG-Nitro-L-arginine

et al. 2005

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Abstract. We evaluated the effects of Rikkunshi-to and several of its ingredients on the delay of gastric emptying induced by a nitric oxide (NO) synthase inhibitor,After oral administration of L-NNA to rats, the gastric emptying rate at 24 h was decreased from 82.8 ± 2.4% to 53.3 ± 5.7%. The decrease of the gastric emptying rate induced by L-NNA treatment was markedly ameliorated by administration of Rikkunshi-to (250 and 500 mg / kg, p.o.) in a dose-dependent manner. To identify the active ingredient of Rikkunshi-to, the components were separated according to polarity, and the effects of the respective fractions on gastric emptying were evaluated. Significant efficacy was found in the water and methanol fractions, but not in the 50% aqueous-methanol fraction. Furthermore, hesperidin (1 -4.29 mg / kg, p.o.) contained in the methanol fraction and L-arginine (4.5 mg / kg, p.o.) contained in the water fraction ameliorated the decrease in the gastric emptying rate induced by L-NNA treatment. These results suggest that Rikkunshi-to ameliorated abnormalities of NO-mediated gastric functions such as delayed gastric emptying, and hesperidin and L-arginine were identified as two of the active ingredients contributing to the ability of Rikkunshi-to to facilitate gastric emptying.

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“…This might appear puzzling, as 5-HT 4 agonists are in general considered strong prokinetic drugs in the entire gastrointestinal tract (9). Similarly, cisapride and other 5-HT 4 agonists have been shown to consistently accelerate gastric emptying in rodents and humans (42,43). This might be due to the dosing regimen used here or the formulation of the drug used.…”

Section: Tablementioning

confidence: 95%

Effects of the neurokinin-1 antagonist maropitant on canine gastric emptying assessed by radioscintigraphy and breath test

Schmitz

Fink²,

Failing³

et al. 2016

Tierarztl Prax Ausg K

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Effects of SK-951, a Benzofuran Derivative, as a Prokinetic Agent in Rats and Dogs.

Cited by 13 publications

References 25 publications

Oral Mitemcinal (Gm‐611), an Erythromycin‐derived Prokinetic, Accelerates Normal and Experimentally Delayed Gastric Emptying in Conscious Dogs

Oral Mitemcinal (Gm‐611), an Erythromycin‐derived Prokinetic, Accelerates Normal and Experimentally Delayed Gastric Emptying in Conscious Dogs

Effects of Rikkunshi-to, a Traditional Japanese Medicine, on the Delay of Gastric Emptying Induced by NG-Nitro-L-arginine

Effects of the neurokinin-1 antagonist maropitant on canine gastric emptying assessed by radioscintigraphy and breath test

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