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Related Experiment Videos

Phenothiazine effect on gastrointestinal tract function.

K Sriram, W Schumer, S Ehrenpreis

    American Journal of Surgery
    |January 1, 1979
    PubMed
    Summary
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    Phenothiazines like chlorpromazine cause paralytic ileus by blocking intestinal neuromuscular function. This effect in guinea pigs was reversed by physostigmine, offering potential treatment insights for gastrointestinal disorders.

    Area of Science:

    • Pharmacology
    • Gastroenterology
    • Neuroscience

    Background:

    • Phenothiazines, such as chlorpromazine (CPZ), are widely used for mental and neurological disorders.
    • Clinical observations show these drugs induce ileus, a condition characterized by gastrointestinal pseudoobstruction and delayed transit.
    • Postoperative patients on CPZ experience prolonged ileus, highlighting a significant clinical concern.

    Purpose of the Study:

    • To investigate the mechanism by which phenothiazines disrupt gastrointestinal motility.
    • To explore potential pharmacological agents for reversing phenothiazine-induced ileus.
    • To establish a preclinical model of phenothiazine-induced paralytic ileus.

    Main Methods:

    • Guinea pigs received intraperitoneal injections of chlorpromazine (CPZ) daily for 5–17 days.

    Related Experiment Videos

  • In vitro studies examined the effect of CPZ on electrically stimulated longitudinal muscle-myenteric plexus preparations.
  • Physostigmine (PGM), an anticholinesterase, was administered to assess reversal of CPZ effects.

    • Main Results:

    • CPZ administration led to cessation of intestinal and colonic peristalsis and cecal distension in guinea pigs.
    • In vitro, phenothiazines blocked the neuromuscular response of the intestine to electrical stimulation for at least 24 hours.
    • Physostigmine successfully reversed the CPZ-induced neuromuscular blockade when the block was less than 80%.

    Conclusions:

    • Phenothiazines impair gastrointestinal neuromuscular function, leading to paralytic ileus.
    • The paralytic ileus observed in the guinea pig model closely mimics the condition in humans.
    • Anticholinesterase agents like physostigmine show potential for reversing phenothiazine-induced ileus.