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Propofol binding site

PostPosted: Mon Sep 23, 2013 2:45 am
by Inventor

Re: Propofol binding site

PostPosted: Tue Sep 24, 2013 11:09 am
by dms407
""Normally, an anesthetic drug binds to the GABAA receptor transiently," Franks explained. "But for the purposes of this research, we wanted to create an analogue that behaved exactly like propofol except that we could activate this chemical hook to permanently bind the drug to the receptor."

So if they can create and analogue that attaches permanently to the receptor, and if the effects of the anesthetic (including any beneficial effects for patients with ALS) are temporary, could they then create an analogue that permanently attaches to the receptor and permanently delivers the benefits?

Re: Propofol binding site

PostPosted: Tue Sep 24, 2013 12:49 pm
by sixwings
Very interesting. I have some caveats, though. The deficiency observed in the GABA-A alpha-1 receptors of ALS patients is a logical target for therapeutic drugs. However, there are good reasons to suppose that GABA-A deficiency is not common to all ALS patients. This is why propofol works for some but not others. Still, I disagree with the claim that the effect of propofol is as short lasting as they make it out to be. Various reports from those who have tried it point to a beneficial effect (e.g., a recovery of a lost function) lasting up to a month or more. So, it's certain that propofol can continue to cause the potentiation of GABA-A receptors long after the hypnotic effect is gone. What this research is showing is that it should be possible to make the potentiation permanent, which would be an enormous breakthrough.

That being said, my biggest problem with propofol is that it is a weak potentiator of the Glycine alpha-1 receptors. This is why I recommend anesthetics like sevoflurane instead of propofol. Hopefully, it's very likely that the same research will apply to other anesthetics as well.