Linked Life Data

19146924

Source:http://linkedlifedata.com/resource/pubmed/id/19146924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-2-11
pubmed:abstractText
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disease. Drugs used in this disease need to cross the blood-brain barrier (BBB). Only riluzole is approved for ALS treatment. We have investigated riluzole as a breast cancer resistance protein (BCRP) substrate by studying its brain transport in CF1 mdr1a (-/-) mice and its intracellular uptake on BeWo cells (human placental choriocarcinoma cell line). We have also investigated the effect of riluzole on BCRP expression level and on its activity using the prazocin as a test probe for brain transport and intracellular uptake. Assays on mdr1a (-/-) mice and BeWo cells showed a higher uptake of riluzole when pretreated with a BCRP inhibitor. After repeated doses of riluzole, BCRP activity was increased in CF1 mdr1a (-/-) mice, riluzole uptake was decrease and both BCRP expression and activity were increased in BeWo cells. In conclusion, we report in this study that riluzole is transported by BCRP at the BBB level and can enhance its function. These results taken with our previous studies on riluzole and P-glycoprotein show that drug-drug interactions between riluzole and efflux transporters substrates may occur at the BBB level and should be taken into account in future clinical trial design in ALS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
452
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-6
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Interactions between riluzole and ABCG2/BCRP transporter.
pubmed:affiliation
Université Paris-Sud XI, Laboratoire de Barrières et Passage des Médicaments, EA 2706, Faculty of Pharmacy, Chatenay-Malabry, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't