Chloral Hydrate

Matt Jones jonesmat at ohsu.edu
Wed Jul 5 14:29:11 EST 1995


In article <C.Hinrichsen-0307951048520001 at mg1_122.plant.utas.edu.au>
Colin Hinrichsen, C.Hinrichsen at anat.utas.edu.au writes:
>I have an experiment going involving testing the response to hypoxia in
>rats and requiring recovery of the animals for a week or so.  I would be
>grateful for some information on the CNS effects of chloral hydrate (or
>whether there is some better anaesthetic agent that I can use).  I cannot
>use pentobarbital because of its depression nor urethane because the
>animals do not recover nor ketamine because of its glutamate antagonism. 
>Gaseous anaesthetics are out because of the need to administer hypoxic
gas
>mixtures.
>Many thanks

The active substance in chloral hydrate anesthesia is the  metabolite
trichloroethanol (TCEt). TCEt is a phenomenally efficacious potentiator
of fast GABAergic inhibitory transmission at anesthetic concentrations
(Lovinger, et al. JPET 264: 1097). Potentiation of GABA-A mediated
inhibition is IMHO the central mechanism by which general anesthetics
produce  anesthesia (with some exceptions, eg. ketamine) (see Zimmerman
et al. JPET 270: 987 for a summary of gen. anesth. effects on GABA-A
receptor currents). So nearly all the agents you could choose will share
a number of common effects that can't be avoided easily: depression of
reflexes and locomotion, analgesia, sedation or unconciousness, amnesia,
etc. These are part of the anesthetic syndrome itself. Additional
effects, such as respiratory or cardiac depression, may vary with the
agent used, and these side effects are probably what you will need to pay
most attention to in trying to optimize your anesthesia. You may find it
useful to review a current clinical anesthesia text to choose an agent
that minimizes side effects that would interfere with your hypoxia
experiment. One potent, fast onset and offset agent with minimal side
effects is propofol (Diprivan or Deprivan, or something like that; see
Hales & Lambert, Br. J. Phar 104: 619 for GABA-A effects). This one might
be worth considering.



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