Reducing alcohol toxicity with alcohol dehydrogenase inhibitors

[Neuroprotection]

The drug 4methyl pirazole has been developed for the treatment of ethylene glycol and methanol poisoning. However it is very expensive at the moment, and most hospitals are reluctant to stock up on it even though a study showed its use would cost far less than the extensive monitoring needed when administering ethanol for treating toxic alcohol poisoning.
This relatively new drug is actually A small molecule with the chemical formula C4H6N2.
If the drug becomes generic or is synthesised in a lab, I wonder if it could be used to reinforce the positive effects of alcohol while eliminating negative symptoms such as hangovers and acetaldehyde toxicity. I am also aware that other enzymes metabolise ethanol but what if we could inhibit them to? Although this may increase the addictive potential of alcohol it may also benefit alcoholics that are on willing to kick the habit acting as a harm reduction technique
What do you think

 

[BurritoJimmy]

Id pay a lot of money for a hangover cure. And I wish ethanol really did treat alcohol poisoning then the motto just drink more and your problems will go away really would be true.

 

[MrRoot]

Well fomepizole (=4-methylpirazole) does reduce hangovers but it also has to be administered shortly after one had taken alcohol if one wants to prevent hangover by tampering with dehydrogenasis.

Hospitals should stock this as it is a part of WHO list of essential medicines. Unless that hospital is in some backwater developing country.

 

[Neuroprotection]

Well fomepizole (=4-methylpirazole) does reduce hangovers but it also has to be administered shortly after one had taken alcohol if one wants to prevent hangover by tampering with dehydrogenasis.

Hospitals should stock this as it is a part of WHO list of essential medicines. Unless that hospital is in some backwater developing country.

Administering the drug after alcohol is fine how about mixing it into the alcoholic drink. How do you think it would enhance the alcohol experience, and do you have any personal experience with it?

 

[Neuroprotection]

Anyone else have any idea on this topic, I know it's all theoretical but it is good if we discuss it and get these ideas out there for researchers.

 

[Neuroprotection]

I've heard that fomepizole was investigated as an alternative treatment for alcoholics, analogous to the nasty deterrent drug disulphiram which causes severe hangovers when consumed with alcohol, through inhibition of aldehyde dehydrogenase. However fomepizole, has no activity on aldehyde dehydrogenase and instead acts as a potent alcohol dehydrogenase inhibitor. Therefore unlike disulphiram, fomepizole not only failed to deter drinking, But run the risk of reinforcing the behaviour by allowing alcoholics to become intoxicated at lower doses and without negative consequences from ethanol.
Personally I have never consumed alcohol and I never will for religious reasons, but I must say fomepizole sounds brilliant to me. Even though I am against alcohol consumption, I would like to ensure that people who choose to drink have a range of harm reduction techniques available to them including substances that affect ethanol metabolism.

 

[Neuroprotection]

It seems this topic is a difficult one and there appears to be a lack of information on and enthusiasm for scientific research on fomepizole, on the part of medical researchers. However I am hoping Bluelighters can help by making Bluelights Research team aware of this topic. I would do this myself but unfortunately my blindness makes it very difficult if not impossible.
I strongly believe that altering alcohol metabolism to bypass the formation of toxic alldihides would greatly reduce damage associated with alcohol consumption.
To demonstrate the role of aldehydes as toxic metabolites, we can consider the alcohol methanol. Methanol itself is very similar to drinking alcohol aka ethanol chemically and farmocologically. However methanol is extremely toxic if ingested. Early symptoms of methanol exposure are no different than ethanol intoxication. However at the time ethanol would by causing a painful hangover, methanol would by inducing blindness, kidney and brain damage and respiratory failure at the mitochondrial level leading to death in many cases.
These dreadful affects are not the direct actions of methanol itself, but those of its metabolite formaldehyde and possibly formic acid.

 

[JacksinPA]

Fomepizole is 4-methylpyrazole. See [/FONT][/COLOR]https://en.wikipedia.org/wiki/Fomepizole. Fomepizole is a competitive inhibitor of the enzyme alcohol dehydrogenase,^[4] found in the liver. It is administered by IV.

Concurrent use with ethanol is contraindicated because fomepizole is known to prolong the half-life of ethanol. Extending the half-life of ethanol may increase and extend the intoxicating effects of ethanol, allowing for greater (potentially dangerous) levels of intoxication at lower doses. Better things for better living through chemistry.

It is available either by prescription or from research chemical supply houses as the HCl salt. Ref: Li, T.-K., and Theorell, H. Acta Chem. Scand. 23, 892, (1969)