Literature DB >> 17572097

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.

Pascale Jolliet1, Stéphane Nion, Gwenaëlle Allain-Veyrac, L Tilloy-Fenart, Dorothée Vanuxeem, Vincent Berezowski, Roméo Cecchelli.   

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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Year:  2006        PMID: 17572097     DOI: 10.1016/j.phrs.2006.12.004

Source DB:  PubMed          Journal:  Pharmacol Res        ISSN: 1043-6618            Impact factor:   7.658


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