Steroidal neuromuscular blocking agents

Since 1964 approximately 20 steroidal neuromuscular blocking agents have been evaluated clinically. Pancuronium, a bisquaternary compound designed on the drawingboard, was the first steroidal relaxant introduced into clinical practice worldwide in the 1970's. Although a major improvement, pancuronium was still a potent, long-acting agent with moderate cardiovascular effects. The search for a potent cardiovascularly "clean" compound with a shorter time course has resulted in the development of pancuronium's monoquaternary derivative, vecuronium. Vecuronium gained widespread popularity in the 1980's due to its intermediate duration and lack of side-effects. However, its 3-hydroxy metabolite is also a potent neuromuscular blocker and may contribute to neuromuscular block after long periods of vecuronium administration. Further research was directed towards the development of compounds with a faster onset of action. In 1994 the vecuronium analog, rocuronium, was introduced, a less potent compound with a rapid onset and intermediate duration and without a pharmacologically active metabolite. Rocuronium is the first non-depolarizing relaxant which allows intubation within 60-90 seconds of its administration. Recently, a relatively low potency, fast onset and short-acting vecuronium analog, Org 9487, has been selected to undergo clinical evaluation as a potential alternative for succinylcholine. Org 9487 combines early satisfactory intubating conditions with a short time course and early reversibility at the cost of moderate cardiovascular effects.</p