Interactions between antiparkinsonian drugs and ABCB1/P-glycoprotein at the blood-brain barrier in a rat brain endothelial cell model
Identifieur interne : 002518 ( Main/Exploration ); précédent : 002517; suivant : 002519Interactions between antiparkinsonian drugs and ABCB1/P-glycoprotein at the blood-brain barrier in a rat brain endothelial cell model
Auteurs : Sarah Vautier [France] ; Aline Milane [France] ; Christine Fernandez [France] ; Marion Buyse [France] ; Helene Chacun [France] ; Robert Farinotti [France]Source :
- Neuroscience letters [ 0304-3940 ] ; 2008.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
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 ofantiparkinsonian 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 ICso of 6.71 μM on Rhodamine 123 uptake and an IC50 of 1.71 μM on digoxine uptake. Thus, bromocriptine at 100 μM 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.
Affiliations:
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Antiparkinson agent</term>
<term>Blood brain barrier</term>
<term>Bromocriptine</term>
<term>Drug interaction</term>
<term>Encephalon</term>
<term>Endothelial cell</term>
<term>Glycoprotein</term>
<term>Models</term>
<term>Rat</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Antiparkinsonien</term>
<term>Glycoprotéine</term>
<term>Barrière hématoencéphalique</term>
<term>Encéphale</term>
<term>Cellule endothéliale</term>
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<front><div type="abstract" xml:lang="en">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 ofantiparkinsonian 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 ICso of 6.71 μM on Rhodamine 123 uptake and an IC<sub>50</sub>
of 1.71 μM on digoxine uptake. Thus, bromocriptine at 100 μM 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.</div>
</front>
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<tree><country name="France"><region name="Île-de-France"><name sortKey="Vautier, Sarah" sort="Vautier, Sarah" uniqKey="Vautier S" first="Sarah" last="Vautier">Sarah Vautier</name>
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<name sortKey="Buyse, Marion" sort="Buyse, Marion" uniqKey="Buyse M" first="Marion" last="Buyse">Marion Buyse</name>
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<name sortKey="Farinotti, Robert" sort="Farinotti, Robert" uniqKey="Farinotti R" first="Robert" last="Farinotti">Robert Farinotti</name>
<name sortKey="Farinotti, Robert" sort="Farinotti, Robert" uniqKey="Farinotti R" first="Robert" last="Farinotti">Robert Farinotti</name>
<name sortKey="Fernandez, Christine" sort="Fernandez, Christine" uniqKey="Fernandez C" first="Christine" last="Fernandez">Christine Fernandez</name>
<name sortKey="Fernandez, Christine" sort="Fernandez, Christine" uniqKey="Fernandez C" first="Christine" last="Fernandez">Christine Fernandez</name>
<name sortKey="Milane, Aline" sort="Milane, Aline" uniqKey="Milane A" first="Aline" last="Milane">Aline Milane</name>
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