Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents

Anesthesiology. 2015 Dec;123(6):1337-49. doi: 10.1097/ALN.0000000000000868.


Background: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation.

Methods: The 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.

Results: In 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.

Conclusions: Calabadion 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstanols / antagonists & inhibitors
  • Animals
  • Atracurium / analogs & derivatives
  • Atracurium / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Male
  • Neostigmine / pharmacology
  • Neuromuscular Nondepolarizing Agents / antagonists & inhibitors*
  • Rats
  • Rocuronium
  • Sugammadex
  • Sulfonic Acids / pharmacology*
  • Vecuronium Bromide / antagonists & inhibitors
  • gamma-Cyclodextrins / pharmacology*


  • Androstanols
  • Heterocyclic Compounds, 4 or More Rings
  • Neuromuscular Nondepolarizing Agents
  • Sulfonic Acids
  • calabadion 1
  • gamma-Cyclodextrins
  • Atracurium
  • Sugammadex
  • Neostigmine
  • Vecuronium Bromide
  • cisatracurium
  • Rocuronium