Help needed: chemistry of alcohol addiction

Matt Jones jonesmat at ohsu.edu
Tue Mar 26 13:50:57 EST 1996


In article <4j7mu3$99m at news.ycc.yale.edu> Peter Bell,
bell at morpheus.cis.yale.edu writes:
>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....  

Blood alcohol levels of EtOH after a six pack probably approach *40
millimolar* or more!
This is about an order of magnitude higher than anesthetic concentrations
of volatile anesthetics like halothane. 

Comments from the soapbox:
General anesthetics like barbiturates and volatiles have dramatic effects
on GABA-A receptor mediated synaptic transmission in nearly all
preparations studied, *at clinically relevant concentrations*. Ethanol,
by contrast, has effects that vary with preparation. In some preps (e.g.
embryonic cultured hippocampal neurons), hundreds of millimolar EtOH is
totally without effect on GABA-A receptors, whereas in others 40 mM EtOH
potentiates GABAergic transmission quite well. These "discrepancies"
might be due to preparation-specific combinations of GABA receptor
subunits, or to EtOH interacting with different
phosphorylation/dephosphorylation processes in a tissue-specific manner
(c.f., Wafford and Whiting (1992) FEBS Lett. 313:113-117; or Weiner et
al. (1994) JPET 268:1388-1395). 

Ethanol has pretty robust effects on NMDA receptors, too. It blocks them
in a non-competitive manner, I think. It does this at quite reasonable
concentrations (e.g. Lovinger et al. (1990) Ann. Med. 22:247-252). 

It also affects AMPA and 5HT-3 receptors (see other papers by David
Lovinger, or Forrest Weight and colleagues), and probably nicotinic
receptors (Haydon? Dilger?) and calcium channels (can't think of a ref
off hand, but I bet there're plenty).

It's floating around at huge concentrations in drunk people, so it's
probably getting on a lot of receptors and channels. Probably the only
thing it's *NOT* doing is directly permeabilizing membranes, whatever
that means. 

Thanks for your patience,
-Matt



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