TABLE 1

Examples of P-gp multidrug resistance reversal agents

GenerationRepresentative AgentMechanisms of ActionClinical ResponseReference
FirstVerapamil; reserpine; quinine; tamoxifen; cyclosporine A; toremifeneAltering ATP hydrolysis pathway (tariquidar; verapamil; cyclosporine A; toremifene; quinine; tamoxifen); competition for binding sites (verapamil; reserpine; quinine; elacridar; cyclosporine A); alteration in P-gp expression (verapamil; cyclosporine A; valspodar)Toxicities; nephrotoxicity, myelosuppression, and neurotoxicityVarma et al., 2003
SecondDexverapamil; valspodar; biricodarMore affinity, efficacy; low toxicity and interaction with cytochrome P450 enzymesKathawala et al., 2015
ThirdElacridar; laniquidar; zosuquidar; dofequidar; mitotane; annamycin; tariquidarMore specific and potent with diminutive pharmacokinetic interactionsPusztai et al., 2005