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Enzymatic pathways in chloral hydrate metabolism?

Limpet_Chicken

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In the early stages of metabolism of chloral hydrate, which enzyme is responsible for conversion of CH to 1,1,1-trichloroethanol? In particular, I'm wondering what effect inhibition of alcohol dehydrogenase might have on the conversion of chloral hydrate to it's active metabolite?

Also, is CH strictly a prodrug to trichloroethanol, or is the glycol form itself active at GABAaRs to any appreciable extent?

Asking mainly because I've just come upon 100g of AR-grade chloral hydrate; it was purchased primarily, for the preparation of Melzer's reagent, a mixture based on iodine, potassium or sodium iodide and chloral hydrate as the 'active ingredients', used for testing samples of fungal spores, which may give three kinds of color-changing reaction, and is a vital tool in identification of some fungi, but given it's analytical grade, figured I might as well try it a few times, as well as keep a little in reserve for days where sleep is otherwise impossible, such as when my pain meds run low, as then, even heavy benzo doses won't reliably put me to sleep (e.g 70mg nitrazepam, and I'd still be awake, although feeling much better, still not able to sleep, unless I use the nitrazepam alongside chlormethiazole)

Alcohol on the other hand will quite reliably put me out, although only for a couple of hours, and at the price of a foul hangover if I were to drink enough to make me sleep more than 3-4 hours at most in a day, but unlike most GABAergics, it DOES make me sleep if I've little opioids left in my system, so hopefully chloral hydrate will do the same, if I'm ever in need of it in that context.

What I'm wondering though is if the alcohol dehydrogenase inhibiting effects of chlormethiazole (no, I'm not going to be combining it and chloral hydrate together), after the chlormethiazole's GABAergic effects have worn off, will interfere with metabolism of the diol to trichloroethanol? how long does the enzyme inhibition last after a dose of chlormethiazole?

Just giving the stuff an exploratory try atm, it's been a long time since I mucked about with chloral or it's analogs for anything other than use in Melzer's, 1g, stuffed into an oversized gelcap is proving not to be overpowering, but definitely a pleasant relaxation, alongside 6omg IR oxy, insufflated and a shot of morphine (can't remember how much, prepared it last night but ended up going to sleep and saving it for today, and no, I'm not reccommending people mix depressants and opioids, but I'm opioid tolerant, being a chronic pain patient, I have to take them or go into W/D)

Feels like..the equivalent of 4-5 shots of spirit or so, maybe 3-4, but between 3-4 and 4-5 shots, weighed accurately in a scale with accuracy down to 1mg, dose of chloral-1001mg (couldn't be bothered trying to remove 1mg from the measured out quantity, since it would have absolutely no relevance whatsoever considering the dose range of chloral hydrate)
 
In the early stages of metabolism of chloral hydrate, which enzyme is responsible for conversion of CH to 1,1,1-trichloroethanol? In particular, I'm wondering what effect inhibition of alcohol dehydrogenase might have on the conversion of chloral hydrate to it's active metabolite?

probably EC 1.1.1.2 aldehyde dehydrogenase which is alcohol dehydrogenase running backward.
doing aldehyde + NADPH------->alcohol + NADP
https://enzyme.expasy.org/EC/1.1.1.2

stictly speaking chloral hydrate glycol form is an aldehyde and it probably is somewhat active on its own. Chloral hydrate and plain alcohol causes death quite frequently through depression and alcohol would inhibit the conversion of chloral hydrate to 2,2,2-Trichloroethanol.

next question is how much does chlormethiazole inhibit alcohol dehydrogenase and is it competitive inhibition.
 
I20, 3.1 mM, I50 6 mM via CYP2E1 inhibition - refs? My cat told me :)

For actual first-hand knowledge, LC is the guy who has played with clomethiazole and it's analogues. Ask him - he's a very reasonable person when it comes to even handed adult discussion of a subject, I'm sure you will get on like a house on fire :) mea culpa, tenui Perlucidus Pullum.
 
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I might be, but, I wouldn't very well be making a thread to search for information I already had.
 
next question is how much does chlormethiazole inhibit alcohol dehydrogenase and is it competitive inhibition.

I rather don't do assumption, but hypothetically it could also ..

be the next question from LC as he is also taking Clomethiazole. But interpreting his answer that's probably not it.

Or a eastern egg type of warning from novaveritas ment to LC to also take the Clo into the picture.
But assuming never ends and most frequenltly are mer assumptions. But curious to but mainly in the effects of all that obscure downers.
 
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