Bookmark and Share
BioAssay: AID 624098

Assay for General Anesthetic Phenotype in Xenopus Tadpoles

Anesthetic development has remained a largely empirical process. There are growing concerns about the cognitive effects of known general anesthetics [1] and acceleration of the onset of neurodegenerative disease [2]. The compounds' toxicity [3] and multiple specific binding targets in the mammalian brain [4] has made them less attractive as drug leads. This assay was designed for the in vivo follow-up testing of compounds in tadpoles. ..more
_
   
 Tested Compounds
 Tested Compounds
All(27)
 
 
Active(6)
 
 
Inactive(17)
 
 
Inconclusive(4)
 
 
 Tested Substances
 Tested Substances
All(27)
 
 
Active(6)
 
 
Inactive(17)
 
 
Inconclusive(4)
 
 
AID: 624098
Data Source: NCGC (APOF0913)
BioAssay Type: Primary, Primary Screening, Single Concentration Activity Observed
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-04-13
Hold-until Date: 2013-03-01
Modify Date: 2013-03-01

Data Table ( Complete ):           Active    All
Target
BioActive Compounds: 6
Depositor Specified Assays
AIDNameTypeComment
2385Probe Development Summary for Identification of Novel General AnestheticssummaryProbe Development Summary for Identification of Novel General Anesthetics
2323qHTS Validation Assay for Identification of Novel General AnestheticsconfirmatoryValidation apoferritin assay run on SigmaAldrich LOPAC1280 collection
485281qHTS Assay for Identification of Novel General AnestheticsconfirmatoryqHTS Assay for Identification of Novel General Anesthetics
489008Confirmation Assay for Identification of Novel General AnestheticsconfirmatoryConfirmation Assay for Identification of Novel General Anesthetics
Description:
Anesthetic development has remained a largely empirical process. There are growing concerns about the cognitive effects of known general anesthetics [1] and acceleration of the onset of neurodegenerative disease [2]. The compounds' toxicity [3] and multiple specific binding targets in the mammalian brain [4] has made them less attractive as drug leads. This assay was designed for the in vivo follow-up testing of compounds in tadpoles.

References:

[1] S.L. Bianchi, T. Tran, C. Liu, S. Lin, Y. Li, J.M. Keller, R.G. Eckenhoff, and M.F. Eckenhoff, Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 29 (2008) 1002-10.

[2] Z. Xie, Y. Dong, U. Maeda, R.D. Moir, W. Xia, D.J. Culley, G. Crosby, and R.E. Tanzi, The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci 27 (2007) 1247-54.

[3] P. Honegger, and J.M. Matthieu, Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures. J Neurosci Res 45 (1996) 631-6.

[4] M.F. Eckenhoff, K. Chan, and R.G. Eckenhoff, Multiple specific binding targets for inhaled anesthetics in the mammalian brain. J Pharmacol Exp Ther 300 (2002) 172-9.

[5] C.A. Butts, J. Xi, G. Brannigan, A.A. Saad, S.P. Venkatachalan, R.A. Pearce, M.L. Klein, R.G. Eckenhoff, and I.J. Dmochowski, Identification of a fluorescent general anesthetic, 1-aminoanthracene. Proc Natl Acad Sci U S A 106 (2009) 6501-6.

[6] W.A. Lea, J. Xi, A. Jadhav, L. Lu, C.P. Austin, A. Simeonov, and R.G. Eckenhoff, A high-throughput approach for identification of novel general anesthetics. PLoS One 4 (2009) e7150.
Protocol
Pre-limb bud Xenopus tadpoles were obtained in large batches from Nasco, Inc. Batches of 10 tadpoles were placed in 20 mm Petri dishes with approximately 20 ml of pond water ("pond water" is approximately a 20-fold dilution of Ringers saline solution). Compounds were added to the pond water from DMSO stock to obtain 100, 10 and 1 microM concentrations. Tadpoles were then incubated with these solutions for 1 hour, and then scored for "anesthesia". Anesthesia in this case is lack of movement in response to a sharp tap on the Petri dish lid, i.e., a lack of startle response. This correlates well to the loss of righting reflex in rodents and the loss of consciousness in humans. The pond water is then changed, and the return of a startle response is monitored for 24 hours. Immobility at 24 hours is considered death.
Comment
Compound Ranking:

Compounds were considered active if "Percent Immobility at 10uM after 1hr" was greater than 50, inclusive if between 15 and 50, and inactive if less than 15.

PUBCHEM_ACTIVITY_SCORE for actives or inconclusives were set to same as the "Percent Immobility at 10uM at 1hr" and was set to 0 if compound was categorized as inactive.

"Percent Immobility at 10uM at 24hr" represents toxicity. Higher percent immobility implies toxicity.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Percent Immobility at 10uM after 1hr% tadpole immobility at 10uM after 1 hrFloat%
2Percent Immobility at 10uM after 24hr% tadpole immobility at 10uM after 24 hoursFloat%
Additional Information
Grant Number: MH084836

Data Table (Concise)
PageFrom: