IUBio

What is the pharmacological basis of urethane anestehsia ?

Matt Jones jonesmat at ohsu.edu
Thu May 30 11:18:15 EST 1996


In article <4oir2c$l46 at styx.uwa.edu.au> Dr. Alex,
aledain at receptor.pharm.uwa.edu.au writes:
>The pharmacological basis? This debate has been going on for decades! It 
>smacks of a semester paper ... 

Yes, there is definitely some controversy about the mechanisms of general
anesthesia. However, IMHO, the great majority of correlative evidence
comes down in favor of anesthetics acting by potentiating GABA-A
receptor-mediated inhibition. True, they do other things as well. But
*almost* all general anesthetics potentiate GABA receptor currents at the
appropriate concentrations, which can not really be said for
glutamatergic processes. Also, the correlation between in vivo anesthetic
potency and GABA-ergic potentiation is approximately as good as that
between anesthetic potency and lipid solubility (Zimmerman et al., JPET,
270:987-991). The advantage of the GABA hypothesis over the lipid
perturbation hypothesis is that the former accounts for why anesthetics
produce anesthesia, and the latter does not (by now you can probably
guess what I did my thesis work on).

Urethane potentiates GABA-activated currents quite well at the
concentrations used to induce anesthesia (see Zimmerman et al.). This
should probably be kept in mind when interpreting data from urethane
anesthetized animals. 

Cheers,
-Matt



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