TABLE 1.
Substrates and Inhibitors of ABC Transporters that Are Expressed at the Blood-Brain Barrier
| ABC Transporter | Substrates | Inhibitors |
|---|---|---|
| P-glycoprotein (ABCB1) | Anticancer drugs e.g., Doxorubicine, daunorubicine, vinblastine, vincristine, etoposide, teniposide, paclitaxel, methotrexate | 1st Generation e.g., verapamil, cyclosporin A, quinidine, quinine, amiodarone, detergents such as cremophore EL |
| Immunosuppressive agents e.g., Cyclosporin A | 2nd Generation e.g., PSC-833 (valspodar), GF120918 (elacridar), VX-710 (biricodar), dexverapamil | |
| Corticoids e.g., Dexamethasone, hydrocortisone, corticosterone, cortisol, aldosterone | 3rd Generation e.g., OC 144-093 (ONT-093), LY335979 (zosuquidar), XR9576 (tariquidar), R101933 (laniquidar), GF120918 | |
| Analgesics e.g., Morphine | ||
| HIV protease inhibitors e.g., Amprenavir, indinavir, saquinavir | ||
| Cytokines e.g., IL-2, IL-4, IFN-γ | ||
| Antidiarrheal agents e.g., Loperamide | ||
| Anthelminthic agents e.g., Ivermectin, abamectin | ||
| Anti-gout agents e.g., Colchicines | ||
| Histamine H2-receptor antagonists e.g., Cimetidine | ||
| Calcium channel blocker e.g., verapamil | ||
| Antiepileptic drugs e.g., Phenytoin, carbamazepine, lamotrigine, phenobarbital, felbamate, gabapentin, topiramate | ||
| Antiemetics e.g., Domperidone, ondansetron | ||
| Cardiac glycosides e.g., Digoxin | ||
| Diagnostic (fluorescent) dyes e.g., Rhodamine-123 | ||
| Antidepressants e.g., Amitryptiline, nortryptiline, doxepin, venlafaxine, paroxetine | ||
| Antibiotics e.g., Erythromycin, valinomycin, tetracyclines, fluoroquinolines | ||
| MRP1 (ABCC1) | Anticancer drugs e.g., Etoposide, teniposide, vincristine, doxorubicine, daunorubicine, methotrexate; Leukotriene C4 (LTC4), D4, E4; Various glutathione, glucuronide, and sulfate conjugates, but also unconjugated compounds (e.g., fluorescein) | Sulfinpyrazone, probenecid, MK571, LTC4, some Pgp inhibitors (e.g., cyclosporin A, verapamil, PSC 833) |
| MRP2 (ABCC2) | Similar to MRP1 | Similar to MRP1 |
| MRP3 (ABCC3) | Organic anion transporter with considerable overlap in drug substrates with MRP1 and MRP2 | Classical organic anion transport inhibitors such as sulfinpyrazone, indomethacin, and probenecid |
| MRP4 (ABCC4) | Anticancer drugs such as methotrexate, 6-mercaptopurine, thioguanine | |
| MRP5 (ABCC5) | cGMP, cAMP, 6-mercaptopurine, thioguanine, fluorescein | Probenecid and phosphodiesterase inhibitors such as trequensin or sildenafil |
| MRP6 (ABCC6) | BQ-123 (an anionic cyclopentapeptide and endothelin receptor antagonist) | |
| BCRP (ABCG2) | Several anticancer drugs; considerable overlap with Pgp, MRP1, and MRP2. Anthracyclines, mitoxantrone, bisantrene, the camptothecins topotecan and SN-38, prazosin | GF120918 (inhibits also Pgp), fumitremorgin C (FTC) and FTC analogues such as Ko132 and Ko134, CI1033 |