One of the hottest topics in epileptology: ABC proteins. Their inhibition may be the future for patients with intractable seizures.
One of the new topics in epileptology is the ABC proteins, which seem to control whether or not anti-epileptic drugs (AEDs) can come in contact with and affect the epileptogenic areas that cause seizures. The goal of this report is to simplify the concepts involved in these proteins and then to review the progress made in the field, especially of one protein called P-glycoprotein (P-gp). First, the ABC proteins are reviewed, mainly P-gp, which appears to alter drug permeability (like an extra blood-brain barrier). The possibility is discussed that changes in P-gp are the result of many seizures; are caused by the AEDs, or truly reflect pharmacoresistance. The different locations where these changes can be seen include the endothelial cells, glia and also neurons. The polymorphism of P-gp, called C3435T, probably has little functional significance and finally the importance of inhibitors of P-g to reverse pharmacoresistance is emphasized. Tariquidar (XR9576) is likely to be a good candidate that appears to inhibit these proteins and therefore to allow the AEDs to control the intractable seizures that may account for nearly 40% of our patients.
Hughes
John R
JR
Department of Neurology, University of Illinois Medical Center, 912 S. Wood Street, Chicago, IL 60612, USA. jhughes@uic.edu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018432:Drug Resistance, Multiple / Q000235:genetics; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D011804:Quinolines; C402343:tariquidar