Paralysis was maintained in sheep by computer-controlled infusion of atracurium, using the integrated electromyogram as a measure of neuromuscular transmission. A number of experiments were conducted to ascertain the average infusion rate required to achieve a given level of paralysis for one hour. Each experiment yielded a point on a plot of paralysis versus infusion rate. A dose-response curve based upon a simple model of drug receptor interaction at the neuromuscular junction was fitted to the experimental points by least squares and is able to provide a useful explanation of clinically observed behaviour. The recovery time was also measured in each experiment and plotted against both prior level of paralysis and prior average infusion rate.
Exploring Drug-Receptor Interaction Kinetics: Lessons from a Sigma-1 Receptor Transmembrane Biosensor