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.