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→Mechanisms of Anesthesia
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJyYaI:ACTRDVEAAAAAasZ0eaKpU14jFRxgeJubQZ-AUJs&scisig=ACTRDVEAAAAAasZ0eT0zDfaBVoegO8FEa7bX0-A&scisf=4&ct=citation&cd=-1&hl=en 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor. Based on 30 years of in vitro studies (n>330), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
*[https://scholar.googleusercontent.com/scholar.bib?q=info:dK96wvRnWFAJ:scholar.google.com/&output=citation&scisdr=CiBKb9IEEIjgixJyYaI:ACTRDVEAAAAAasZ0eaKpU14jFRxgeJubQZ-AUJs&scisig=ACTRDVEAAAAAasZ0eT0zDfaBVoegO8FEa7bX0-A&scisf=4&ct=citation&cd=-1&hl=en 2026 A&A paper] argues that classifying anesthetics as, say, GABAergic vs. NMDAergic is misleading. Propofol for instance actually has higher potency at the α4β2 nAChR and HCN1 receptors than at the "classic" GABA<sub>A</sub>R receptor. Based on 30 years of in vitro studies (n>330), most anesthetics exhibit similar potency across a range of receptors. Most receptors are non-selective for ligands. What this paper addresses but doesn't answer is whether the receptors are present at the correct locations and necessary to the anesthetic behavioral response.
*According to this paper, some anesthetics (i.e. ketamine, dexmedetomidine, etomidate, benzos) are fairly selective, but are rarely used as sole anesthetics. Below, I list each of the ''in vitro'' binding affinities of these "selective" anesthetics, up until there is a change of one order of magnitude or greater for the next receptor.
*According to this paper, some anesthetics (i.e. ketamine, dexmedetomidine, etomidate, benzos) are fairly selective, but are rarely used as sole anesthetics. Below, I list each of the ''in vitro'' binding affinities of these "selective" anesthetics, up until there is a change of one order of magnitude or greater for the next receptor.
**Ketamine binds to α4β4 nAChR w/ IC<sub>50</sub> of 0.144 uM, but has an IC<sub>50</sub> for the GluN1/N2C NMDAR of 0.338 uM.
**Ketamine binds
**Dexmedetomidine binds to α<sub>2A</sub> AR w/ K<sub>D</sub> of 0.0014 uM and the M<sub>3</sub> mAChR w/ IC<sub>50</sub> of 0.001 uM.
***α4β4 nAChR, IC<sub>50</sub> 0.144 uM
**Etomidate binds to α1β2γ2 GABA<sub>A</sub>R w/ an EC<sub>50</sub> of 1.08 uM, but to I<sub>K(dr)</sub> with an IC<sub>50</sub> of 4.59 uM, and the α1 GlyR w/ an IC<sub>50</sub> of 5.37 uM.
***GluN1/N2C NMDAR, IC<sub>50</sub> 0.338 uM
**Midazolam binds to α1β2γ2 GABA<sub>A</sub>R, between the α1 and γ2 subunits, w/ EC<sub>50</sub> of 0.041 uM, Na<sub>V</sub> (neuron) IC<sub>50</sub> of 0.074 uM, and nAChR (muscle) w/ IC<sub>50</sub> of 0.143 uM.
**Dexmedetomidine binds
***α<sub>2A</sub> AR, K<sub>D</sub> 0.0014 uM
***M<sub>3</sub> mAChR, IC<sub>50</sub> 0.001 uM
**Etomidate binds
***α1β2γ2 GABA<sub>A</sub>R, EC<sub>50</sub> 1.08 uM
***I<sub>K(dr)</sub>, IC<sub>50</sub> 4.59 uM
***α1 GlyR, IC<sub>50</sub> 5.37 uM
**Midazolam binds
***α1β2γ2 GABA<sub>A</sub>R, between the α1 and γ2 subunits, EC<sub>50</sub> 0.041 uM
***Na<sub>V</sub> (neuron), IC<sub>50</sub> 0.074 uM
***nAChR (muscle), IC<sub>50</sub> 0.143 uM
**Diazepam binds to '''α1β2γ2 GABA<sub>A</sub>R''' w/ EC<sub>50</sub> of 0.07 uM.
**Diazepam binds to '''α1β2γ2 GABA<sub>A</sub>R''' w/ EC<sub>50</sub> of 0.07 uM.
**Sevoflurane binds to '''K<sub>v</sub>1.2''' w/ EC<sub>50</sub> of 0.0097 mM.
**Sevoflurane binds to '''K<sub>v</sub>1.2''' w/ EC<sub>50</sub> of 0.0097 mM.