• Friederike Haerter, Jeroen Cedric Peter Simons, Urs Foerster, Ingrid Moreno Duarte, Daniel Diaz-Gil, Shweta Ganapati, Katharina Eikermann-Haerter, Cenk Ayata, Ben Zhang, Manfred Blobner, Lyle Isaacs, and Matthias Eikermann.
• From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (F.H., J.C.P.S., I.M.D., D.D.-G., M.E.); Clinic of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany (U.F., M.B.); Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland (S.G., B.Z., L.I.); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (K.E.-H., C.A.); and Department of Anesthesia and Critical Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.E.).
• Anesthesiology. 2015 Dec 1;123(6):1337-49.

BackgroundThe authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation.MethodsThe dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine.ResultsIn vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate.ConclusionsCalabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.

This article appears in the collections: Neuromuscular myths: the lies we tell ourselves and What are Calabadions? Can they replace sugammadex?.

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