Atracurium: conception and inception.

The rationale underlying the design of atracurium, a bis-quaternary ammonium neuromuscular blocking agent which incorporates the Hofmann elimination as a novel biodegradation pathway, is described. Destruction in vivo, of the bis-quaternary structure essential for neuromuscular blocking activity, by the combination of Hofmann elimination and a parallel ester hydrolysis leads to innocuous breakdown products that are without neuromuscular or cardiovascular effects and to a time-course of action which is unaffected by the level of plasma esterase activity, renal or hepatic function.