Although alkyl-qac are potent in vitro inhibitors, they are not viable as therapeutic drugs because of their high toxicity risks at the concentrations required for therapeutic efficacy. Furthermore, symmetric alkyl-qac lack specificity to human Kir molecular species of particular physiological functions (targeting multiple Kir channels and/or physiological off-targets should be avoided) and have shown pharmacokinetic limitations including reduced absorption, distribution, metabolism, and/or excretion.