Cyclodextrins and the emergence of sugammadex

Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.