Indeed, because laudanosine is cleared primarily via renal excretion, a cat study modelling anephric patients went so far as to corroborate that EEG changes, when observed, were evident only at plasma concentrations 8 to 10 times greater than those observed in humans during infusions of atracurium. Thus, the cat study predicted that, following atracurium administration in an anephric patient, laudanosine accumulation and related CNS or cardiovascular toxicity were unlikely - a prediction that correlated very well with a study in patients with kidney failure and undergoing cadaveric renal transplantation. Furthermore, almost a decade later, work by Cardone et al.. confirmed that, in fact, it is the steroidal neuromuscular-blocking agents pancuronium and vecuronium that, when introduced directly into the CNS, were likely to cause acute excitement and seizures, owing to accumulation of cytosolic calcium caused by activation of acetylcholine receptor ion channels. Unlike the two steroidal agents, neither atracurium nor laudanosine caused such accumulation of intracellular calcium. Just over two decades later with availability of atracurium, there is little doubt that laudanosine accumulation and related toxicity will likely never be seen with the doses of atracurium that are generally used.Laudanosine is also a metabolite of cisatracurium that, because of its identical structure to atracurium, undergoes chemodegradation via Hofmann elimination in vivo. Plasma concentrations of laudanosine generated are lower when cisatracurium is used. Pharmacokinetics
Atracurium is susceptible to degradation by Hofmann elimination and ester hydrolysis as components of the in vivo metabolic processes.
Stenlakes research group advanced this  concept by systematically synthesizing numerous quaternary ammonium β-aminoesters and β-aminoketones and evaluated them for skeletal muscle relaxant activity: one of these compounds, initially labelled as 33A74, eventually led to further clinical development, and came to be known as atracurium. References
External links
Neuromuscular+blocking+agents at the US National Library of Medicine Medical Subject Headings (MeSH)
"Atracurium besilate". Drug Information Portal. U.S. National Library of Medicine.