Comparison of the effects of T-1815, yohimbine and naloxone on mouse colonic propulsion.
The colonic prokinetic activity of a newly synthesized compound, T-1815, administered orally, was compared with that of yohimbine and naloxone in mice. The time required to evacuate a glass bead inserted into the distal colon was taken as an index of prokinetic activity. Clonidine (3-30 micrograms/kg s.c.), and loperamide (0.3-3.0 mg/kg s.c.) delayed bead expulsion in a dose-dependent manner. Yohimbine (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) showed a dose-dependent reduction of the delay in evacuation induced by clonidine, but naloxone had no effect. The loperamide-induced retardation of colonic propulsion was reduced by naloxone (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) in a dose-dependent manner, but yohimbine had no effect. In normal animals, yohimbine and naloxone had no significant effect on evacuation, while a slight acceleration was observed with T-1815 at 10 mg/kg. No soft feces and/or diarrhea were observed with any of the three test drugs. These results indicate that T-1815 appears to be a unique colonic prokinetic compound, the action of which may be mediated through mechanisms other than antagonism for alpha 2-adrenoceptors or opioid receptors.
Yamada
K
K
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Onoda
Y
Y
D000284:Administration, Oral; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors; D003106:Colon / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008139:Loperamide / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D011437:Propylamines; D013876:Thiophenes; C081988:T 1815; D015016:Yohimbine; D009270:Naloxone; D008139:Loperamide; D003000:Clonidine