Organic anion, organic cation and zwitterion transporters of the SLC22 and SLC47 superfamily (OATs, OCTs, OCTNs and MATEs)

There are 23 transporter proteins in the SLC22 family, which are divided into several subgroups including the organic cation transporters (OCTs), the carnitine/organic cation transporters (OCTNs), the organic anion transporters (OATs) and the urate transporter 1 (URAT1). Although the MATE1/SLC47A1 and MATE2/SLC47A2 transporters belong to the SLC family, they are efflux transporters localized on the apical membrane of organ barriers. Inhibition of a multidrug and toxin extrusion (MATE) transporter may be clinically relevant for DDIs with oral antidiabetic drugs, in addition to the inhibition of uptake transporters OCTs, such as metformin DDIs. Regulatory agencies require that DDI risks of OCT2, OAT1 and OAT3 are evaluated in drug development. MATE inhibition may decrease the renal clearance of metformin, thus contributing to the clinical drug interactions with OCT2. It is emerging that this transporter should be evaluated during drug development. OCT3 is preferentially expressed in brain regions that belong to monoamine pathways and it is considered to play an important role in stress and in the pathogenesis of depression; it has potential to become a new antidepression drug target. Co-administration of OAT inhibitors could reduce the uptake of antiviral drugs by proximal tubule cells and decrease the renal clearance of these drugs, which could be used clinically to prevent nephrotoxicity. URAT1-meditated urate reabsorption is inhibited by uricosuric drugs and is of clinical importance in treating gout. URAT1 is an important pharmacological target for novel uricosuric drugs.