Multidrug and Toxin Extrusion Transporter 1 Inhibitors

MATE1 (SLC47A1) is a multidrug efflux pump that functions as a proton/organic cation antiporter and sits on the apical membrane, where it plays a physiological role in the excretion of cationic compounds - endogenous metabolites, drugs and toxins - through the kidney and liver, into urine and bile respectively. It is the exit step of a two-transporter route: the organic cation transporters OCT1 (SLC22A1) and OCT2 (SLC22A2) are both recorded on the basolateral membrane of hepatocytes and proximal tubules, taking cations up out of the blood, and MATE1 then pumps them out of the cell. Drugs in this class inhibit that exit step, so the substrate cation accumulates. FDA's drug-interaction table lists cimetidine and pyrimethamine as in vitro MATE1 inhibitors, and metformin, creatinine, MPP+ and tetraethylammonium as in vitro MATE1 substrates. The cited MED-RT class is not a useful membership list here: it holds only lofexidine.