title: Calabadion: A new agent to reverse the effects of benzylisoquinoline and steroidal neuromuscular-blocking agents.
abstract: BACKGROUND
  To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  After 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.
  
  
  CONCLUSIONS
  Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Martina
authors.initials: M
authors.lastname: Grosse-Sundrup
authors.forename: Katharina
authors.initials: K
authors.lastname: Eikermann-Haerter
authors.forename: Sebastina
authors.initials: S
authors.lastname: Zaremba
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.forename: Da
authors.initials: D
authors.lastname: Ma
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
authors.forename: Matthias
authors.initials: M
authors.lastname: Eikermann
mesh_terms: D000732:Androstanols / Q000037:antagonists & inhibitors; D000818:Animals; D001279:Atracurium / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D044182:Benzylisoquinolines / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D019148:Neuromuscular Blockade / Q000379:methods; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077123:Rocuronium; D013451:Sulfonic Acids / Q000494:pharmacology*; D000099246:Cucurbit(n)urils
chemical_list: D000732:Androstanols; D001279:Atracurium; D044182:Benzylisoquinolines; D006576:Heterocyclic Compounds, 4 or More Rings; D047028:Macrocyclic Compounds; D009466:Neuromuscular Blocking Agents; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium; D013451:Sulfonic Acids; D000099246:Cucurbit(n)urils; C583725:calabadion 1; C101584:cisatracurium