Multidrug resistance-associated protein is involved in the... : NeuroReport (original) (raw)
NEUROPHARMACOLOGY AND NEUROTOXICOLOGY
Multidrug resistance-associated protein is involved in the regulation of extracellular levels of phenytoin in the brain
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, 30559 Hannover, Germany
CACorresponding Author
Received 10 May 2001; accepted 25 May 2001
Abstract
The mechanisms that lead to drug resistance in epilepsy are not known. Recently, overexpression of multidrug transporters, such as multidrug resistance-associated protein (MRP), has been reported in surgically resected epileptogenic human brain tissue and suggested to contribute to the drug resistance of epilepsy. However, it is not known to what extent multidrug transporters such as MRP are involved in transport of antiepileptic drugs. In the present study, we used in vivo microdialysis in rats to study whether the concentration of phenytoin in the extracellular fluid of the cerebral cortex can be enhanced by inhibition of MRP, using the MRP inhibitor probenecid. Local perfusion with probenecid via the microdialysis probe significantly enhanced the extracellular concentration of phenytoin. The data indicate that MRP critically participates in the regulation of extracellular brain concentrations of the major antiepileptic drug phenytoin.
© 2001 Lippincott Williams & Wilkins, Inc.