Interactions between antiparkinsonian drugs and ABCB1/P-glycoprotein at the blood-brain barrier in a rat brain endothelial cell model.
Parkinson's disease is a neurodegenerative disorder that requires treatment by dopaminergic agonists, which may be responsible for central side effects. We hypothesized that the efflux transporter ABCB1/P-glycoprotein played a role in brain disposition of antiparkinsonian drugs and could control central toxicity. We aimed to evaluate antiparkinsonian drugs as ABCB1 substrates and/or inhibitors in rat brain endothelial cells GPNT, in order to predict potential clinical drug-drug interactions. Among the antiparkinsonian drugs tested, levodopa, bromocriptine, pergolide and pramipexole were ABCB1 substrates. However, only bromocriptine could inhibit ABCB1 functionality with an IC(50) of 6.71 microM on Rhodamine 123 uptake and an IC(50) of 1.71 microM on digoxine uptake. Thus, bromocriptine at 100 microM is responsible for an increase of levodopa intracellular transport of about 2.05-fold versus control. Therefore, we can conclude that bromocriptine is a potent drug for medicinal interactions in vitro. Hence, in patients with Parkinson's disease, these results may be considered to optimise treatments individually.
Vautier
Sarah
S
Université Paris-Sud XI, Department of Clinical Pharmacy, EA 2706, 5 rue Jean-Baptiste Clement, Châtenay-Malabry 92296, France. sarahvautier@hotmail.com
Milane
Aline
A
Fernandez
Christine
C
Buyse
Marion
M
Chacun
Helene
H
Farinotti
Robert
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects*; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000978:Antiparkinson Agents