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Line 54: − + − *Propofol binds to α4β2 nAChR with IC<sub>50</sub> of 3.13 uM, HCN1 receptors with IC<sub>50</sub> of 4.19 uM, and α1β2γ2 with EC<sub>50</sub> of 5.44 uM.+ + Line 86:
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→Promiscuous Molecular Targets
**Diazepam binds '''α1β2γ2 GABA<sub>A</sub>R''', EC<sub>50</sub> 0.07 uM
**Diazepam binds '''α1β2γ2 GABA<sub>A</sub>R''', EC<sub>50</sub> 0.07 uM
**Sevoflurane binds '''K<sub>v</sub>1.2''', EC<sub>50</sub> 0.0097 mM
**Sevoflurane binds '''K<sub>v</sub>1.2''', EC<sub>50</sub> 0.0097 mM
*Remimazolam binds GABA<sub>A</sub> receptors [https://scholar.googleusercontent.com/scholar.bib?q=info:ZcRExfhIAgQJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJ14Lg:ACTRDVEAAAAAasZz-Lg_XypnrGdHd1YvgyClzzA&scisig=ACTRDVEAAAAAasZz-GKPI-Z0ueEzxZoNZQpLFsU&scisf=4&ct=citation&cd=-1&hl=en non-selectively] (i.e. αxβ2γ2)
*Some common anesthetics that are less selective, or not characterized in the paper
**Propofol binds to α4β2 nAChR with IC<sub>50</sub> of 3.13 uM, HCN1 receptors with IC<sub>50</sub> of 4.19 uM, and α1β2γ2 with EC<sub>50</sub> of 5.44 uM.
**Remimazolam binds GABA<sub>A</sub> receptors [https://scholar.googleusercontent.com/scholar.bib?q=info:ZcRExfhIAgQJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJ14Lg:ACTRDVEAAAAAasZz-Lg_XypnrGdHd1YvgyClzzA&scisig=ACTRDVEAAAAAasZz-GKPI-Z0ueEzxZoNZQpLFsU&scisf=4&ct=citation&cd=-1&hl=en non-selectively] (i.e. αxβ2γ2)
====Probing Anesthetic-Receptor Interactions====
====Probing Anesthetic-Receptor Interactions====
*'''Are there pharmacological agents with effects opposite of anesthetics and with receptor specificity? Do they cross the blood brain barrier? Search [https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL63354/ ChEMBL].'''
*'''Are there pharmacological agents with effects opposite of anesthetics and with receptor specificity? Do they cross the blood brain barrier? Search [https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL63354/ ChEMBL].'''
**'''Search [https://flybase.org flybase], [https://www.informatics.jax.org/ MGI], [https://www.wormbase.org/ wormbase], [https://zfin.org/ zebra fish information network], [https://www.yeastgenome.org/ yeast genome database]'''
**'''Search [https://flybase.org flybase], [https://www.informatics.jax.org/ MGI], [https://www.wormbase.org/ wormbase], [https://zfin.org/ zebra fish information network], [https://www.yeastgenome.org/ yeast genome database]'''
*'''Where and by what cell types are these receptors expressed in the human brain?'''
*'''Where and by what cell types are these receptors expressed in the human brain?'''
===Non-Receptor Mediated Hypothesis===
===Non-Receptor Mediated Hypothesis===
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.
*Hamilton has a gap junction (network of gap junctions?) and some specific neurons that he think are a conserved mechanism of anesthesia. He wants to test this by doing a screen of a bunch of different anesthetics in WT and KO worms with a behavioral screening assay. He has a behavior rig that basically automatically records swimming speed. He wants to look for the EC50 of various anesthetics and see if that number is shifted with KO or KD of different gap junctions.