Probenecid is a benzoic acid derivative that inhibits organic anion transporters (OATs) but activates the transient receptor potential (TRP) channel TRPV1. It inhibits OAT1, OAT3, and OAT6 with Ki values of 6.3, 9.0, and 8.4 μM, respectively, as well as OAT2 with an IC50 value of 0.67 μM. It is a poor inhibitor of the organic cation transporters OCT1 and OCT2 (IC50 = 1.6 and 1.7 mM, respectively). Through its effects on OATs, probenecid enhances the renal excretion of urate, alleviating gout, while reducing the elimination of many medications. It also acts as an agonist of TRPV2 (EC50 = 31.9 μM), eliciting nociceptive behavior under inflammatory conditions in mice.
