Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.
Synapse. 2016-03-15; 70(6): 231-239
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1. Synapse. 2016 Jun;70(6):231-9. doi: 10.1002/syn.21889. Epub 2016 Mar 15.
Permeability of blood-brain barrier in macaque model of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.
Thiollier T(1)(2)(3), Wu C(4), Contamin H(1), Li Q(5)(6), Zhang J(4), Bezard
(1)Cynbiose, Marcy l’Etoile, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000,
(3)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux,
(4)Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing,
People’s Republic of China, 100050.
(5)Motac Neuroscience, Manchester, United Kingdom.
(6)Institute of Laboratory Animal Sciences, China Academy of Medical Sciences,
Beijing, People’s Republic of China.
Brain bioavailability of drugs developed to address central nervous system
diseases is classically documented through cerebrospinal fluid collected in
normal animals, i.e., through an approximation as there are fundamental
differences between cerebrospinal fluid and tissue contents. The fact that
disease might affect brain availability of drugs is almost never considered at
this stage although several conditions are associated with blood-brain barrier
damage. Building upon our expertise in Parkinson’s disease translational
research, the present study addressed this gap comparing plasma and cerebrospinal
fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine,
lovastatin, and simvastatin, in healthy and
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard
model of Parkinson’s disease. The drugs were selected based upon their
differential transport across the blood-brain barrier. Interestingly, brain
bioavailability of quinidine was decreased while others were unaffected.
Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson’s
disease might thus be performed in healthy animals unless the drugs are known to
interact with the organic cation transporter.
© 2016 Wiley Periodicals, Inc.
PMID: 26799359 [Indexed for MEDLINE]