MadSci Network: Medicine |
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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