A Novel Concept of Reversing Neuromuscular Block: Chemical Encapsulation of Rocuronium Bromide by a Cyclodextrin-Based Synthetic Host The discovery of Org 25969 is the result of teamwork with contributions from a number of scientists both inside Organon and outside the company. We would like in particular to acknowledge the following scientists for their invaluable contributions: E. Hutchinson, D. Stevenson, R. Roy, and J. Pick for scaling-up the synthesis; F. Hope, S. Miller, and R. Mason for various in vitro and in vivo pharmacological testing; R. Watson, B. Montgomery, P. Desmond, and A. Osprey for all their analytical effort; and R. McGuire and J. Mestres for graphical presentation of the X-ray crystal structure of the Org 25969–rocuronium complex (Figure 3). We would also like to thank Prof. A. Cooper of Glasgow University who has critically reproduced our calorimetry data of Org 25969–rocuronium complexation (Figure 2).

Abstract

Superior to current clinically used reversal agents in terms of efficacy and side effects: The formation of a high-affinity host–guest binary complex (association constant Ka: ca. 107 M−1) between the aminosteroidal guest molecule rocuronium bromide, the most widely used neuromuscular blocking agent in surgery, and a cyclodextrin-based synthetic host molecule (see X-ray crystal structure) results in reversal of the neuromuscular blockade induced by rocuronium bromide.