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MITEMCINAL (GM‐611), AN ORALLY ACTIVE MOTILIN RECEPTOR AGONIST, IMPROVES DELAYED GASTRIC EMPTYING IN A CANINE MODEL OF DIABETIC GASTROPARESIS
Author(s) -
Onoma Mitsu,
Ozaki Kenichi,
Yogo Kenji,
Monnai Makoto,
Muramatsu Hiroyasu,
Kamei Kenshi,
Kawabe Yoshiki,
Hayashi Shuji,
Shiga Toshihiko,
Matsuo Saori,
Suzuki Masami,
Itoh Zen,
Ōmura Satoshi,
Takanashi Hisanori
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.04924.x
Subject(s) - gastric emptying , medicine , cisapride , motilin , gastroparesis , agonist , endocrinology , diabetes mellitus , oral administration , insulin , vagus nerve , gastroenterology , stomach , receptor , stimulation
SUMMARY1 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 comapred 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 comapred 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.