In light of this, it is important to investigate this topic more fully in order to improve our understanding of the factors associated with AKI in association with these medications, in order to better risk stratify patients receiving them and to develop evidence-based interventions to prevent this serious complication. The potency, longevity of BoNT intoxication has facilitated use of BoNTs as therapeutic agents and the ease with which these toxins can be produced make them potential bioweapons and bioterrorism agents. Overdose with BoNT therapeutics can also result in systemic botulism. BoNTs are the only toxin group in the six most dangerous biothreat agents listed by Centers for Disease Control and Prevention. BoNTs are synthesized as,150-kDa single-chain protoxins that are post translationally processed by proteolytic cleavage to form a disulfide-linked dimer, composed of a 100-kDa heavy chain and a 50-kDa light chain. The HC comprises a 50- kDa C-terminal domain that participates in the binding of toxin to productive ectoacceptors on the cell surface of peripheral cholinergic nerve cells and the 50-kDa N-terminal domain of the HC facilitates the translocation of the LC across an CGP 60474 endosomal membrane into the cytosol of the nerve cell. SNARE proteins are essential for exocytosis of neurotransmitter and cleavage of these protein by BoNT inhibits the release of acetylcholine from synaptic terminals leading to neuromuscular paralysis or botulism. The most effective immunotherapy for protection against BoNTs relies on vaccination with pentavalent toxoid species, although supplies are reserved for high-risk individuals. Moreover vaccination of general Ceranib 1 public also restricts subsequent BoNT��s therapeutic applications, if needed. There are no therapies available for BoNT mediated post neuronal intoxication. The current treatments for BoNT poisoning are limited to: the administration of antitoxin to neutralize and clear toxin from the circulation which is not effective in post neuronal intoxication and, therefore, would be of limited use following an act of bioterror ; and mechanical ventilation which is necessary once BoNT-induced paralysis compromises thoracic muscle contraction. However, the latter form of treatment would also be impractical, even a limited act of bioterror employing BoNT, as critical care resources would likely to be overwhelmed. The estimated cost for treating a botulism patient with such intensive care could be as high as $350,000. Antibody therapy can be very effective; it has several limitations, including limited availability, lot-to-lot potency, variability and short window of application. Thus, the hypothesis rationalizing a small-molecule based therapeutic approach for the treatment of BoNT/A-LC intoxication is as follows: Small drug like molecules can penetrate into the neuronal cytosol and inhibit the toxin��s proteolytic activity during post neuronal intoxication.