Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier

Pharmacol Res. 2007 Jul;56(1):11-7. doi: 10.1016/j.phrs.2006.12.004. Epub 2006 Dec 19.

Abstract

Purpose: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS).

Methods: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells.

Results: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study.

Conclusions: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antiemetics / metabolism
  • Antiemetics / pharmacokinetics*
  • Blood-Brain Barrier / metabolism*
  • Brain / cytology
  • Brain / metabolism
  • Capillary Permeability
  • Cells, Cultured
  • Chlorpromazine / metabolism
  • Chlorpromazine / pharmacokinetics*
  • Claudin-1
  • Coculture Techniques / methods
  • Domperidone / metabolism
  • Domperidone / pharmacokinetics*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Isonipecotic Acids / metabolism
  • Isonipecotic Acids / pharmacokinetics*
  • Membrane Proteins / analysis
  • Metoclopramide / metabolism
  • Metoclopramide / pharmacokinetics*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Occludin
  • Phosphoproteins / analysis
  • Rats
  • Sucrose / metabolism
  • Tight Junctions / chemistry
  • Tight Junctions / metabolism
  • Zonula Occludens-1 Protein

Substances

  • Antiemetics
  • Claudin-1
  • Cldn1 protein, rat
  • Isonipecotic Acids
  • Membrane Proteins
  • Occludin
  • Ocln protein, rat
  • Phosphoproteins
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • metopimazine
  • Domperidone
  • Sucrose
  • Metoclopramide
  • Chlorpromazine