Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.
Identifieur interne : 000199 ( Main/Exploration ); précédent : 000198; suivant : 000200Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.
Auteurs : Thibaud Thiollier [France] ; Caisheng Wu ; Hugues Contamin [France] ; Qin Li [Royaume-Uni] ; Jinlan Zhang ; Erwan Bezard [France]Source :
- Synapse (New York, N.Y.) [ 1098-2396 ] ; 2016.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology), Animals, Blood-Brain Barrier (drug effects), Brain (drug effects), Disease Models, Animal, Dopamine (metabolism), Levodopa (pharmacology), Macaca, Male, Parkinson Disease (drug therapy), Parkinson Disease, Secondary (chemically induced), Permeability (drug effects), Pyridines (pharmacology).
- MESH :
- chemical , metabolism : Dopamine.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Levodopa, Pyridines.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Blood-Brain Barrier, Brain, Permeability.
- drug therapy : Parkinson Disease.
- Animals, Disease Models, Animal, Macaca, Male.
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.
DOI: 10.1002/syn.21889
PubMed: 26799359
Affiliations:
- France, Royaume-Uni
- Angleterre, Aquitaine, Grand Manchester, Nouvelle-Aquitaine
- Bordeaux, Manchester
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Le document en format XML
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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.</div></front></TEI><affiliations><list><country><li>France</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Aquitaine</li><li>Grand Manchester</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li><li>Manchester</li></settlement></list><tree><noCountry><name sortKey="Wu, Caisheng" sort="Wu, Caisheng" uniqKey="Wu C" first="Caisheng" last="Wu">Caisheng Wu</name><name sortKey="Zhang, Jinlan" sort="Zhang, Jinlan" uniqKey="Zhang J" first="Jinlan" last="Zhang">Jinlan Zhang</name></noCountry><country name="France"><noRegion><name sortKey="Thiollier, Thibaud" sort="Thiollier, Thibaud" uniqKey="Thiollier T" first="Thibaud" last="Thiollier">Thibaud Thiollier</name></noRegion><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><name sortKey="Contamin, Hugues" sort="Contamin, Hugues" uniqKey="Contamin H" first="Hugues" last="Contamin">Hugues Contamin</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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