Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed gastric emptying in a canine model of diabetic gastroparesis.
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.
Onoma
Mitsu
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan.
Ozaki
Ken-ichi
K
Yogo
Kenji
K
Monnai
Makoto
M
Muramatsu
Hiroyasu
H
Kamei
Kenshi
K
Kawabe
Yoshiki
Y
Hayashi
Shuji
S
Shiga
Toshihiko
T
Matsuo
Saori
S
Suzuki
Masami
M
Itoh
Zen
Z
Omura
Satoshi
S
Takanashi
Hisanori
H
D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D018589:Gastroparesis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists* / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000502:physiology
D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D004917:Erythromycin; C103741:mitemcinal