Calabadion is a new heterocyclic molecule that offers rapid and complete reversal of both aminosteroids, such as rocuronium, and benzylisoquinoline NMBDS, such as cisatracurium.summary
- Ulrike Hoffmann, Martina Grosse-Sundrup, Katharina Eikermann-Haerter, Sebastina Zaremba, Cenk Ayata, Ben Zhang, Da Ma, Lyle Isaacs, and Matthias Eikermann.
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
- Anesthesiology. 2013 Aug 1;119(2):317-25.
IntroductionTo evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects.MethodsA total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure.ResultsAfter the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 ± 1.1 and 16.2 ± 3.3 min with placebo to 4.6 ± 1.8 min with neostigmine/glycopyrrolate to 15 ± 8 and 84 ± 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 ± 2.8 and 9.9 ± 1.7 min with placebo to 2.8 ± 0.8 and 7.6 ± 2.1 min with neostigmine/glycopyrrolate to 47 ± 13 and 87 ± 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h.ConclusionCalabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.
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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