Loperamide effects on hepatobiliary function, intestinal transit and analgesia in mice

A. Hurwitz, M. I. Sztern, G. A. Looney, Z. Ben-Zvi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Loperamide effects on hepatobiliary function, analgesia and gut transit were studied in mice. Varying doses of the antidiarrheal drug, loperamide, were administered to mice by intracerebroventricular, intravenous, subcutaneous and intragastric routes. Gut motility was determined by intestinal transit of India ink, analgesia by warm water tail flick latency, and hepatobiliary function by retention of the anionic dye, sulfobromophthalein in plasma and liver. When given by all routes at modest doses, loperamide slowed intestinal transit. Analgesia, a centrally mediated opiate effect, wa only detected after intracerebroventricular or subcutaneous loperamide at high, near-toxic doses. Elevations of plasma and liver sulfobromopthalein were noted at routes and doses which slowed gut transit, well below those needed for analgesia. Intragastric loperamide at one fortieth its LD50 caused marked elevation of sulfobromophthalein levels and gut slowing, but no analgesia. Sulfobromopthalein elevation and gut slowing by intragastric loperamide were not affected by spinal cord transection but were reversed by naltrexone, an opiate antagonist. Non-toxic doses of loperamide slow gut transit and modify hepatobiliary function in mice by opiate actions at peripheral sites.

Original languageEnglish
Pages (from-to)1687-1698
Number of pages12
JournalLife Sciences
Volume54
Issue number22
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • analgesia
  • gastrointestinal transit
  • hepatobiliary function
  • loperaminde
  • opiates
  • sulfobromophthalein

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