Inhibitory action of chlorpromazine on intestinal movement in mice and its antagonistic agents

Adynamic ileus is a toxic effect produced by chlorpromazine (Chl). The present study is to analyze the inhibitory action of Chl on the intestinal movement of mice and to search its antagonistic remedies. Inhibition was evaluated by 2 tests: the loss of defecation reflex and the inhibited transport of phenol red in the intestinal tract. Chl (1-2 mg.kg-1 i.p. or 1 microgram per mouse i.c.v.) inhibited the intestinal movement powerfully. Scopolamine (Sco 4 mg.kg-1 i.p. or 4-8 micrograms per mouse i.c.v.) produced the same effect. The i.v. ED50 (L95) of Chl and Sco for inhibition of the defecation reflex were 0.85 (0.79-0.93) and 3.49 (3.24-3.78) mg.kg-1, respectively. Haloperidol (1-4 mg.kg-1 i.p.), sulpiride (10 mg.kg-1 i.p.), and phentolamine (2-4 mg.kg-1 i.p. or 4 micrograms per mouse i.c.v.) did not affect the defecation reflex. In the isolated guinea pig ileum the pA2 value of Chl against carbachol (Car) was 4.5 and that of Sco was 9.1. In addition, the inhibitory effect caused by Sco was antagonized by physostigmine (Phy 0.08 mg.kg-1 sc), but not by pilocarpine (Pil 100-200 micrograms per mouse i.c.v.) and 4-aminopyridine (4-AP 1 microgr per mouse i.c.v.), whereas that caused by Chl was antagonized by Pil (100 micrograms per mouse i.c.v.) and 4-AP (1 microgram per mouse i.c.v.), but not by Phy. Neostigmine (Neo 0.05 mg.kg-1 sc) or Car (0.05 mg.kg-1 sc) combined with 4-AP (2 mg.kg-1 sc) exhibited a synergetic effect against Chl-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)