Gastric Emptying in Diabetic Gastroparetic Dogs: Effects of SK-951,a Novel Prokinetic Agent

Takeda, Motohiro; Mizutani, Yusuke; Yamano, Masaya; Tsukamoto, Katsura; Suzuki, Tsunemasa

doi:10.1159/000056068

Cited by 18 publications

(21 citation statements)

References 19 publications

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“…The absorbed tracer materials can be monitored through exhaled air (breath test) or by measuring plasma/serum drug concentrations. One such drug that has been frequently used for this purpose is acetaminophen 13, 14. Acetaminophen is not absorbed from the stomach and can be easily measured in the blood (plasma) of animals.…”

Section: Methods Of Studying Gastric Transit In Dogsmentioning

confidence: 99%

Factors Influencing the Gastric Residence of Dosage Forms in Dogs

Martinez

Papich

2009

Journal of Pharmaceutical Sciences

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Section: Methods Of Studying Gastric Transit In Dogsmentioning

confidence: 99%

Factors Influencing the Gastric Residence of Dosage Forms in Dogs

Martinez

Papich

2009

Journal of Pharmaceutical Sciences

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“…They, of course, should not be used in the subset of patients with rapid gastric emptying. Several other agents have been evaluated for their prokinetic effect, including SK-951, a benzofuran derivative which improves gastric emptying in STZ-induced diabetic dogs,100 and epalrestat, an aldose reductase inhibitor which increases the amplitude of three cycles per minute waves on EGG in patients with diabetic gastroparesis 101. The 5-HT 4 agonists prucalopride and TD-5108 accelerate gastric emptying but have not been tested in gastroparesis 102 103.…”

Section: Treatmentmentioning

confidence: 99%

Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years: Figure 1

Kashyap

Farrugia

2010

Gut

163

127

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Diabetic gastroparesis is a disorder that occurs in both type 1 and type 2 diabetes. It is associated with considerable morbidity among these patients and resultant economic burden on the health system. It is primarily a disease seen in middle aged women though the increased predisposition in women still remains unexplained. Patients often present with nausea, vomiting, bloating, early satiety, and abdominal pain. The pathogenesis of this complex disorder is still not well understood but involves abnormalities in multiple interacting cell types including the extrinsic nervous system, enteric nervous system, Interstitial Cells of Cajal (ICC), smooth muscles and immune cells. The primary diagnostic test remains gastric scintigraphy though other modalities such as breath test, capsule, ultrasound, MRI and SPECT imaging show promise as alternative diagnostic modalities. The mainstay of treatment for diabetic gastroparesis has been antiemetics, prokinetics, nutritional support and pain control. In recent years, gastric stimulation has been used in refractory cases with nausea and vomiting. As we better understand the pathophysiology, newer treatment modalities are emerging which aim to correct the underlying defect. In this review we highlight what has been learned about diabetic gastroparesis in the past 5 years. We review the epidemiology, pathogenesis, diagnosis and treatment of diabetic gastroparesis focusing on the areas that are still controversial and those that require more studies. We also focus on advances in our understanding of the cellular changes that underlie development of diabetic gastroparesis highlighting new opportunities for targeted therapy. Keywords

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“…This method gives a good picture of gastric emptying because paracetamol is not absorbed from the stomach, but is rapidly absorbed from the small intestine 26 . The paracetamol method has been widely used to assess gastric emptying in humans and in several animal species, including dogs 16,18,26,30–36 . However, plasma paracetamol may be affected by liver or renal dysfunction because, after absorption from the small intestine, paracetamol is predominantly metabolised in the liver and excreted from the kidney 37 .…”

Section: Discussionmentioning

confidence: 99%

Mitemcinal (Gm‐611), an Orally Active Motilin Receptor Agonist, Improves Delayed Gastric Emptying in a Canine Model of Diabetic Gastroparesis

Onoma

Monnai²,

Muramatsu

et al. 2008

Clin Exp Pharma Physio

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1. The aim of the present study was to evaluate the effects of mitemcinal (GM-611), an orally active motilin receptor agonist, on delayed gastric emptying in a canine model of diabetic gastroparesis and to compare these effects with those of cisapride. 2. Moderate hyperglycaemia was induced by a single intravenous injection of a mixture of streptozotocin (30 mg/kg) and alloxan (50 mg/kg). Dogs that maintained moderate hyperglycaemia (fasting plasma glucose 200-300 mg/dL) without insulin treatment were selected and gastric emptying in these dogs was determined by the paracetamol method. 3. One year after the onset of diabetes, there was no difference in the gastric emptying of normal and diabetic dogs. However, after 5 years, the diabetic dogs showed delayed gastric emptying. The motor nerve conduction velocity of the tibial nerve was significantly lower in diabetic dogs compared with normal dogs at both time points. 4. Histopathological examination at the end of the study showed that there were fewer nerve fibres in both dorsal vagal and tibial nerves of diabetic dogs compared with normal dogs. The onset of delayed gastric emptying is thought to have occurred gradually, in parallel with abnormal autonomic nerve function induced by the long period of moderate hyperglycaemia. 5. Oral administration of mitemcinal (0.125, 0.25 or 0.5 mg/kg) dose-dependently accelerated delayed gastric emptying, significant at 0.5 mg/kg, in diabetic dogs, whereas cisapride (1, 3 or 10 mg/kg) had no significant effect. These results add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis.

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Gastric Emptying in Diabetic Gastroparetic Dogs: Effects of SK-951,a Novel Prokinetic Agent

Cited by 18 publications

References 19 publications

Factors Influencing the Gastric Residence of Dosage Forms in Dogs

Factors Influencing the Gastric Residence of Dosage Forms in Dogs

Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years: Figure 1

Mitemcinal (Gm‐611), an Orally Active Motilin Receptor Agonist, Improves Delayed Gastric Emptying in a Canine Model of Diabetic Gastroparesis

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