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A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2

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A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2. / Diaz-Gil, Daniel; Haerter, Friederike; Falcinelli, Shane; Ganapati, Shweta; Hettiarachchi, Gaya K; Simons, Jeroen C P; Zhang, Ben; Grabitz, Stephanie D; Moreno Duarte, Ingrid; Cotten, Joseph F; Eikermann-Haerter, Katharina; Deng, Hao; Chamberlin, Nancy L; Isaacs, Lyle; Briken, Volker; Eikermann, Matthias.

In: ANESTHESIOLOGY, Vol. 125, No. 2, 08.2016, p. 333-345.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Diaz-Gil, D, Haerter, F, Falcinelli, S, Ganapati, S, Hettiarachchi, GK, Simons, JCP, Zhang, B, Grabitz, SD, Moreno Duarte, I, Cotten, JF, Eikermann-Haerter, K, Deng, H, Chamberlin, NL, Isaacs, L, Briken, V & Eikermann, M 2016, 'A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2', ANESTHESIOLOGY, vol. 125, no. 2, pp. 333-345. https://doi.org/10.1097/ALN.0000000000001199

APA

Diaz-Gil, D., Haerter, F., Falcinelli, S., Ganapati, S., Hettiarachchi, G. K., Simons, J. C. P., Zhang, B., Grabitz, S. D., Moreno Duarte, I., Cotten, J. F., Eikermann-Haerter, K., Deng, H., Chamberlin, N. L., Isaacs, L., Briken, V., & Eikermann, M. (2016). A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2. ANESTHESIOLOGY, 125(2), 333-345. https://doi.org/10.1097/ALN.0000000000001199

Vancouver

Diaz-Gil D, Haerter F, Falcinelli S, Ganapati S, Hettiarachchi GK, Simons JCP et al. A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2. ANESTHESIOLOGY. 2016 Aug;125(2):333-345. https://doi.org/10.1097/ALN.0000000000001199

Bibtex

@article{f9a2845915fe4441bc9370c8b6beddf2,
title = "A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2",
abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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-{\`a}-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.CONCLUSIONS: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.",
keywords = "Anesthesia, General/methods, Anesthetics, Dissociative/toxicity, Anesthetics, Intravenous/toxicity, Animals, Blood Pressure/drug effects, Cell Survival/drug effects, Electroencephalography/drug effects, Ether-A-Go-Go Potassium Channels/antagonists & inhibitors, Etomidate/antagonists & inhibitors, Heterocyclic Compounds, 4 or More Rings/pharmacology, Ketamine/antagonists & inhibitors, Male, Mutagens/toxicity, Necrosis/prevention & control, Postural Balance/drug effects, Rats, Rats, Sprague-Dawley, Reflex/drug effects, Sulfonic Acids/pharmacology",
author = "Daniel Diaz-Gil and Friederike Haerter and Shane Falcinelli and Shweta Ganapati and Hettiarachchi, {Gaya K} and Simons, {Jeroen C P} and Ben Zhang and Grabitz, {Stephanie D} and {Moreno Duarte}, Ingrid and Cotten, {Joseph F} and Katharina Eikermann-Haerter and Hao Deng and Chamberlin, {Nancy L} and Lyle Isaacs and Volker Briken and Matthias Eikermann",
year = "2016",
month = aug,
doi = "10.1097/ALN.0000000000001199",
language = "English",
volume = "125",
pages = "333--345",
journal = "ANESTHESIOLOGY",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2

AU - Diaz-Gil, Daniel

AU - Haerter, Friederike

AU - Falcinelli, Shane

AU - Ganapati, Shweta

AU - Hettiarachchi, Gaya K

AU - Simons, Jeroen C P

AU - Zhang, Ben

AU - Grabitz, Stephanie D

AU - Moreno Duarte, Ingrid

AU - Cotten, Joseph F

AU - Eikermann-Haerter, Katharina

AU - Deng, Hao

AU - Chamberlin, Nancy L

AU - Isaacs, Lyle

AU - Briken, Volker

AU - Eikermann, Matthias

PY - 2016/8

Y1 - 2016/8

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.

KW - Anesthesia, General/methods

KW - Anesthetics, Dissociative/toxicity

KW - Anesthetics, Intravenous/toxicity

KW - Animals

KW - Blood Pressure/drug effects

KW - Cell Survival/drug effects

KW - Electroencephalography/drug effects

KW - Ether-A-Go-Go Potassium Channels/antagonists & inhibitors

KW - Etomidate/antagonists & inhibitors

KW - Heterocyclic Compounds, 4 or More Rings/pharmacology

KW - Ketamine/antagonists & inhibitors

KW - Male

KW - Mutagens/toxicity

KW - Necrosis/prevention & control

KW - Postural Balance/drug effects

KW - Rats

KW - Rats, Sprague-Dawley

KW - Reflex/drug effects

KW - Sulfonic Acids/pharmacology

U2 - 10.1097/ALN.0000000000001199

DO - 10.1097/ALN.0000000000001199

M3 - SCORING: Journal article

C2 - 27341276

VL - 125

SP - 333

EP - 345

JO - ANESTHESIOLOGY

JF - ANESTHESIOLOGY

SN - 0003-3022

IS - 2

ER -