surgical local and general anesthetics and PAM interaction w benzos and GABAaR

[[cs...]]

Hi all,

 

I had a quick question, and I am hoping someone here can help.  Below is the list of positive allosteric modulators and orthosteric agonists for the GABAa receptor.  In the PAMs list, I see volatile and inhaled anesthetics

 

I have 2 questions regarding the above for surgery.

 

1. Is a local surgical anesthetic considered a PAM given the above info?  Are there any that I can tell the anesthesiologist that are not considered PAMs?

2. I assume a general anesthetic is considered a PAM for the most part (inhaled), but are there any non PAM general anesthetics that can be used during surgery.?               

 

  I don't know if there are any anesthesiologists out there or someone with a strong background in pharmacology in this area, but if so, could you please share your knowledge.?

 

Here is the list I alluded to below.  The orthosteric agonists and the PAMs are listed in bold print.

 

Thanks in advance ......

 

Orthosteric agonists: GABA, gaboxadol, isoguvacine, muscimol, progabide, piperidine-4-sulfonic acid (partial agonist).

 

Orthosteric antagonists: bicuculline, gabazine.

 

Positive allosteric modulators (PAMs): barbiturates, benzodiazepines, certain carbamates (ex. carisoprodol, meprobamate, lorbamate), thienodiazepines, ethanol (alcohol), etomidate, glutethimide, kavalactones,[27] meprobamate, quinazolinones (ex. methaqualone, etaqualone, diproqualone), neuroactive steroids,[28] niacin/niacinamide,[29] nonbenzodiazepines (ex. zolpidem, eszopiclone), propofol, stiripentol,[30] theanine, valerenic acid, volatile/inhaled anesthetics, and lanthanum.[31]

 

Negative allosteric modulators: flumazenil, Ro15-4513, sarmazenil, amentoflavone, and zinc.[32]

 

Second-order modulators: (−)‐epigallocatechin‐3‐gallate.

 

Non-competitive channel blockers: cicutoxin, oenanthotoxin, pentylenetetrazol, picrotoxin, thujone, and lindane