BioMed Research International / 2015 / Article / Tab 1

Review Article

Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

Table 1

Substrates and inhibitors of ABC transporters that are expressed at the blood brain barrier.

ABC transporterSubstratesInhibitors

P-glycoprotein (ABCB1)Anticancer drugs, for example, doxorubicin, daunorubicin, vincristine, etoposide, teniposide, paclitaxel, and methotrexate 1st generation, for example, verapamil, cyclosporine A, quinidine, quinine, amiodarone, and detergents such as Cremophor EL
Immunosuppressive agents, for example, cyclosporine A 2nd generation, for example, PSC-833 (valspodar), GF120918 (elacridar), VX-710 (biricodar), and dexverapamil
Corticoids, for example, dexamethasone, hydrocortisone, corticosterone, cortisol, and aldosterone3rd generation, for example, OC 144-093 (ONT-093), LY335979 (zosuquidar), XR9576 (tariquidar), R101933 (laniquidar), and GF120918
Analgesics, for example, morphine
HIV protease inhibitors, for example, amprenavir, indinavir, and saquinavir
Cytokines, for example, IL-2, IL-4, and IFN-γ
Antidiarrheal agents, for example, loperamide
Anthelminthic agents, for example, ivermectin and abamectin
Antigout agents, for example, colchicines
Histamine H2-receptor antagonists, for example, cimetidine
Calcium channel blockers, for example, verapamil
Antiepileptic drugs, for example, phenytoin, carbamazepine, lamotrigine, phenobarbital, felbamate, gabapentin, and topiramate
Antiemetics, for example, domperidone and ondansetron
Cardiac glycosides, for example, digoxin
Diagnostic (fluorescent) dyes, for example, rhodamine-123
Antidepressants, for example, amitriptyline, nortriptyline, doxepin, venlafaxine, and paroxetine
Antibiotics, for example, erythromycin, valinomycin, tetracyclines, and fluoroquinolones

MRP1 (ABCC1)Anticancer drugs, for example, etoposide, teniposide, vincristine, doxorubicin, daunorubicin, and methotrexate; leukotriene C4 (LTC4), D4, and E4; various glutathione, glucuronide, and sulfate conjugates as well as unconjugated compounds (e.g., fluorescein) Sulfinpyrazone, probenecid, MK571, LTC4, and some P-gp inhibitors (e.g., cyclosporine A, verapamil, and PSC 833)

MRP2 (ABCC2)Similar to MRP1 Similar to MRP1

MRP3 (ABCC3)Organic anion transporter with considerable overlap in drug substrates with MRP1 and MRP2Classical organic anion transport inhibitors, for example, sulfinpyrazone, indomethacin, and probenecid

MRP4 (ABCC4)Anticancer drugs, for example, methotrexate, 6-mercaptopurine, and thioguanine

MRP5 (ABCC5)cGMP, cAMP, 6-mercaptopurine, thioguanine, and fluorescein Probenecid and phosphodiesterase inhibitors, for example, trequinsin or sildenafil

MRP6 (ABCC6)BQ-123 (an anionic cyclopentapeptide and endothelin receptor antagonist)

BCRP (ABCG2)Several anticancer drugs; considerable overlap with P-gp, MRP1, and MRP2. Anthracyclines, mitoxantrone, bisantrene, the camptothecins topotecan
and SN-38, prazosin, BNP1350, tomudex, and chlorine E6
GF120918 (also inhibits P-gp), fumitremorgin C (FTC), and FTC analogs, for example, Ko132, Ko134, CI1033, and estrone

From [13, 5559].