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.
OBJECTIVE
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.
Jolliet
Pascale
P
Laboratoire de Pharmacologie, Faculté de Médecine, 1, Rue Gaston Veil, 44305 Nantes Cedex 01, France. pascale.jolliet@univ-nantes.fr
Nion
Stéphane
S
Allain-Veyrac
Gwenaëlle
G
Tilloy-Fenart
L
L
Vanuxeem
Dorothée
D
Berezowski
Vincent
V
Cecchelli
Roméo
R
D000818:Animals; D000831:Animals, Newborn; D000932:Antiemetics / Q000378:metabolism / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002199:Capillary Permeability; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000378:metabolism / Q000493:pharmacokinetics*; D062445:Claudin-1; D018920:Coculture Techniques / Q000379:methods; D004294:Domperidone / Q000378:metabolism / Q000493:pharmacokinetics*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D007540:Isonipecotic Acids / Q000378:metabolism / Q000493:pharmacokinetics*; D008565:Membrane Proteins / Q000032:analysis; D008787:Metoclopramide / Q000378:metabolism / Q000493:pharmacokinetics*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D013395:Sucrose / Q000378:metabolism; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000932:Antiemetics; D062445:Claudin-1; C568114:Cldn1 protein, rat; D007540:Isonipecotic Acids; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C005260:metopimazine; D004294:Domperidone; D013395:Sucrose; D008787:Metoclopramide; D002746:Chlorpromazine