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. |
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Authors: | Pascale Jolliet Stéphane Nion Gwena?lle Allain-Veyrac L Tilloy-Fenart Dorothée Vanuxeem Vincent Berezowski Roméo Cecchelli |
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Institution: | Laboratoire de Pharmacologie, Faculté de Médecine, 1, Rue Gaston Veil, 44305 Nantes Cedex 01, France. pascale.jolliet@univ-nantes.fr |
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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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