Is bupivacaine a decoupler, a protonophore or a proton-leak-inducer?

This paper deals with the mechanism of bupivacaine uncoupling of oxidative phosphorylation in rat heart mitochondria. By comparison with the effects of QX 572, a permanently charged quaternary amine-type local anesthetic, it is concluded that the effects of bupivacaine and QX 572 may be explained by classical uncoupling behaviour. In the case of bupivacaine this uncoupling effect is mediated through a protonophore-like mechanism, whereas that of QX 572 is simply explained by an electrophoretic uptake.