title: A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2.
abstract: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery.
  
  
  
  To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity.
  
  
  
  Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium-based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate.
  
  
  
  Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.
authors.affiliation: From the Anesthesia, Critical Care and Pain Medicine (D.D.-G., F.H., J.C.P.S., S.D.G., I.M.D., J.F.C., M.E.), Radiology (K.E.-H.), and Biostatistics (H.D.), Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Cell Biology and Molecular Genetics (S.F., G.K.H., V.B.) and Chemistry and Biochemistry (S.G., B.Z., L.I.), University of Maryland, College Park, Maryland; Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts (N.L.C.); and Anesthesia and Critical Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.E.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Diaz-Gil
authors.forename: Friederike
authors.initials: F
authors.lastname: Haerter
authors.forename: Shane
authors.initials: S
authors.lastname: Falcinelli
authors.forename: Shweta
authors.initials: S
authors.lastname: Ganapati
authors.forename: Gaya K
authors.initials: GK
authors.lastname: Hettiarachchi
authors.forename: Jeroen C P
authors.initials: JC
authors.lastname: Simons
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Grabitz
authors.forename: Ingrid
authors.initials: I
authors.lastname: Moreno Duarte
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cotten
authors.forename: Katharina
authors.initials: K
authors.lastname: Eikermann-Haerter
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Chamberlin
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
authors.forename: Volker
authors.initials: V
authors.lastname: Briken
authors.forename: Matthias
authors.initials: M
authors.lastname: Eikermann
mesh_terms: D000768:Anesthesia, General / Q000379:methods*; D000778:Anesthetics, Dissociative / Q000633:toxicity; D018686:Anesthetics, Intravenous / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D005045:Etomidate / Q000037:antagonists & inhibitors / Q000633:toxicity; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D009153:Mutagens / Q000633:toxicity; D009336:Necrosis / Q000517:prevention & control; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D013451:Sulfonic Acids / Q000494:pharmacology*
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D051638:Ether-A-Go-Go Potassium Channels; D006576:Heterocyclic Compounds, 4 or More Rings; D009153:Mutagens; D013451:Sulfonic Acids; C000619669:calabadion 2; D007649:Ketamine; D005045:Etomidate