Help needed: chemistry of alcohol addiction

Peter Bell bell at morpheus.cis.yale.edu
Mon Mar 25 22:05:39 EST 1996


In article <mkirby-2503962014060001 at ntoxlab.ento.vt.edu> mkirby at vt.edu (Mike Kirby) writes:
>eleusis at netcom.com (Eleusis) wrote:
>
>> The best theory going, AFAIK, is that alcohol causes generalized neuronal 
>> membrane depolarization in much the same way that anesthetics work, except 
>> anesthetics do it with a bit more selectivity.
>
>What exactly is AFAIK?  This not a term that I've encountered before in
>the pharmacological or toxicological literature.  As for EtOH mode of

Heheheh.  As Far As I Know....  

>action, EtOH IS classified as a GABA-A agonist and not characterized as a
>having properties similar to anesthetics.  Anesthetics, which I assume
>from your description you're referring to locals, tend to cause block in

No, this is advancing a model in which the ethanol partitions into the 
lipids, as do many *general* anesthetics.  The theory on generals (the 
partition theory, that is) is that they may have relatively nonspecific 
effects which first become manifest in neurons with smaller diameter 
fibers and somata, if I'm remembering it correctly.  An alternative is 
that there are some lipid-accessible binding sites for the anesthetics, 
by *very* broad analogy with batrachatoxin in voltage-dependent sodium 
channels (which is to say, the EtOH binding sites can be thought to be 
low-affinity sites on the GABA receptors which are primarily 
lipid-accessible, if you'd like a Grand Unified Theory.)  

There was a review of this in Science about 4-5 years ago, and I haven't 
followed it too closely since then, so I'm likely misremembering the 
details.  There's also some discussion of this in Goodman and Gilman in 
the discussion of general anesthetics and the introduction of ether.  

Anyone know what the effective molar concentration of the "officially 
intoxicated" EtOH blood level is?  I'm thinking something in the range of 
40 micromolar....  

-=Peter
-- 
bell at minerva.cis.yale.edu | http://pantheon.cis.yale.edu/~bell/bell.html
"Whatever our positions lost in logic might be recovered with invective. 
If you never quit an argument, presumably you never lost." 
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