title: Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.
abstract: 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.
authors.affiliation: Cynbiose, Marcy l'Etoile, France.|Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Thiollier
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, People's Republic of China, 100050.
authors.forename: Caisheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Cynbiose, Marcy l'Etoile, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Contamin
authors.affiliation: Motac Neuroscience, Manchester, United Kingdom.|Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, People's Republic of China, 100050.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000, Bordeaux, France.|Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, People's Republic of China.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D008251:Macaca; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D010539:Permeability / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology
chemical_list: D011725:Pyridines; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine
keywords: Parkinson; bioavailability; blood-brain barrier; cerebrospinal fluid; macaque; pharmacokinetics