Inhibitory action of chlorpromazine on intestinal movement in mice and its antagonistic agents
Xiong, Y.Q.; Li, B.H.
Zhongguo Yao Li Xue Bao 15(3): 235-239
1994
ISSN/ISBN: 0253-9756 PMID: 7976378 Document Number: 436264
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 cntdot kg-1 ip or 1 mu-g per mouse icv) inhibited the intestinal movement powerfully. Scopolamine (Sco 4 mg cntdot kg-1 ip or 4-8 mu-g per mouse icv) produced the same effect. The iv ED-50 (L-95) 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 cntdot kg-1, respectively. Haloperidol (1-4 mg cntdot kg-1 ip), sulpiride (10 mg cntdot kg-1 ip), and phentolamine (2-4 mg cntdot kg-1 ip or 4 mu-g per mouse icv) did not affect the defecation reflex. In the isolated guinea pig ileum the pA-2 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 cntdot kg-11 sc), but not by pilocarpine (Pil 100-200 mu-g per mouse icv) and 4-aminopyridine (4-AP 1 mu-g per mouse icv), whereas that caused by Chl was antagonized by Pil (100 mu-g per mouse icv) and 4-AP (1 mu-g per mouse icv), but not by Phy. Neostigmine (Neo 0.05 mg cntdot kg-1 sc) or Car (0.05 mg cntdot kg-1 sc) combined with 4-AP (2 mg cntdot kg-1 sc) exhibited a synergetic effect against Chl-induced inhibition. The results suggested that the inhibitory effect of Chl on the intestinal movement was produced by preventing the release of acetylcholine from the central nervous system.