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.
Pascale Jolliet  1 ,  Stéphane Nion ,  Gwenaëlle Allain-Veyrac ,  L Tilloy-Fenart ,  Dorothée Vanuxeem ,  Vincent Berezowski ,  Roméo Cecchelli
Affiliations
  • 1. Laboratoire de Pharmacologie, Faculté de Médecine, 1, Rue Gaston Veil, 44305 Nantes Cedex 01, France. [email protected]
PMID: 17572097 DOI: 10.1016/j.phrs.2006.12.004
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.

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