MadSci Network: Medicine
Query:

Re: How does chloroform work on the body?

Date: Mon Jan 26 14:51:39 2004
Posted By: Kevin Caldwell, Faculty, Neurosciences, University of New Mexico
Area of science: Medicine
ID: 1074188940.Me
Message:

This is a great question!  The mechanism of action for drugs that produce 
anesthesia is a fascinating area of neuroscience research.

The precise mechanism by which chloroform produces anesthesia is not 
certain (but, see below for a possible explanation).  This is due, in 
part, to the fact that the mechanism of anesthesia itself is uncertain.  
There are two main theories of how drugs produce anesthesia.  The Meyer 
Overton theory states that anesthetics dissolve in cellular membranes, 
causing structural distortion of the membranes.  The distortion may 
reduce the conduction of a nerve impulse along a nerve cell.  This theory 
is based on the observation that the potency of most anesthetic drugs is 
correlated with their solubility in oil. As an alternative to the Meyer 
Overton theory, it has been proposed that anesthetics interact with 
specific proteins.  Examples of proteins that may be altered by binding 
of an anesthetic are neurotransmitter receptors and ion channels. 
Anesthetics may change the conformation (structure) of the protein.  
Other theories include actions at the interface between proteins and 
lipids.  Here is a link to a brief overview of this subject, and the 
history of anesthesia:
 http://www.anes.upmc.edu/anesnews/volume/2003winter_spring/article
s/focus.
html


One possible mechanism of action for chloroform is that it increases 
movement of potassium ions through certain types of potassium channels in 
nerve cells. A paper by Patel et al. published in Nature Neuroscience 
(May 1999, Volume 2, Number 5, pp. 422-426) shows that chloroform 
activates potassium channels.  This can lead to hyperpolarization of 
membranes.  Hyperpolarization of a nerve cell membrane makes it less 
excitable.  When this occurs presynaptically, it will decrease the 
release of neurotransmitters.  When this effect occurs postsynaptically, 
it reduces the response to a neurotransimitter

In general, most anesthetics enhance inhibitory neurotransmission in the 
brain.  Many of them do this by increasing the actions of the primary 
inhibitory neurotransmitter in the brain, gamma-aminobutyric (GABA).  
Chloroform may also act by increasing GABA neurotansmission.


The history of anesthesia is very interesting.  If you are interested, 
information can be found at the following site:
 http://neuro
surgery.mgh.harvard.edu/History/ether1.htm



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