Journal
ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 14, Issue 4, Pages 1277-1287Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5ob02356d
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Funding
- Maryland Technology Development Corporation
- National Institutes of Health [CA168365]
- Department of Anesthesia, Critical Care, and Pain Medicine
- University of Maryland
- NATIONAL CANCER INSTITUTE [R01CA168365] Funding Source: NIH RePORTER
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An acyclic cucurbit[n] uril (CB[n]) based molecular container (2, a. k. a. Calabadion 2) binds to both amino-steroidal and benzylisoquinolinium type neuromuscular blocking agents (NMBAs) in vitro, and reverses the effect of these drugs in vivo displaying faster recovery times than placebo and the.-cyclodextrin (CD) based and clinically used reversal agent Sugammadex. In this study we have assessed the potential for other drugs commonly used during and after surgery (e.g. antibiotics, antihistamines, and antiarrhythmics) to interfere with the ability of 2 to bind NMBAs rocuronium and cisatracurium in vitro. We measured the binding affinities (K-a, M-1) of twenty seven commonly used drugs towards 2 and simulated the equilibrium between 2, NMBA, and drug based on their standard clinical dosages to calculate the equilibrium concentration of 2 . NMBA in the presence of the various drugs. We found that none of the 27 drugs studied possess the combination of a high enough binding affinity with 2 and a high enough standard dosage to be able to promote the competitive dissociation (a. k. a. displacement interactions) of the 2 . NMBA complex with the formation of the 2 . drug complex. Finally, we used the simulations to explore how the potential for displacement interactions is affected by a number of factors including the K-a of the 2 . NMBA complex, the K-a of the AChR . NMBA complex, the K-a of the 2 . drug complex, and the dosage of the drug.
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