After consuming an adult beverage, alcohol is absorbed into your bloodstream and carried to your liver. There, it is set upon by two enzymes. The first, alcohol dehydrogenase, converts alcohol into acetaldehyde. The second enzyme, aldehyde dehydrogenase, converts the acetaldehyde into acetic acid (the stuff in vinegar) and attaches it to coenzyme A. This two-step process not only detoxifies alcohol, it enables us to use it as an energy source.
Alcohol sensitizers work by inhibiting aldehyde dehydrogenase, causing acetaldehyde to accumulate. This leads to bad times, since acetaldehyde is responsible for many of the negative effects brought about by drinking alcohol. First off, it's carcinogenic, which obviously is lousy. Secondly, if it's able to build up in your body, either because you get really drunk or because you drink moderately but around the same time ingest an inhibitor of aldehyde dehydrogenase, you end up feeling yucky. Your face flushes, your head aches, you feel like puking, you sweat, and/or your heart rate and breathing get a little messed up.
The discomfort caused by alcohol-sensitizing agents, and the subsequent threat of this discomfort, is sufficient to get most people to stop drinking. However, a big issue with using these drugs to treat people with alcohol dependence is they don't reduce the desire to have a drink, so people will often simply choose to stop taking them in order to make booze palatable again.
Disulfiram (trade name Antabuse), perhaps the best known alcohol-sensitizing agent, started out under the name tetraethylthiuram disulfide. First produced in the late 19th century, it was used in the rubber industry to speed up rubber production (specifically, it accelerates vulcanization).
In 1937, an American physician employed at a chemical plant noticed the employees who worked with disulfiram felt lousy after drinking booze. They felt so lousy, in fact, that they gave up drinking entirely. The physician, E. E. Williams, wrote about this effect and suggested putting it to work to help treat alcoholism, but nothing came of it. Around the same time, doctors began using disulfiram to kill the mite responsible for scabies. It seems to mess with the actions of copper-containing enzymes present within mite cells, compromising their ability to generate energy (this kills the mite).
Suspecting it might be toxic to other parasitic animals, the Danish research team of Jens Hald and Erik Jacobsen decided to look into the ability of disulfiram to kill intestinal worms. After establishing its effectiveness in rabbits, Jacobsen decided to dose himself with the drug to see what sort of side effects it tended to cause. As he was unaware of Williams' findings, he popped a couple of pills and went off to a dinner party, shortly after which he felt disgusting. He found he couldn't tolerate any type of alcohol, not even a couple of sips of a light beer. Hald experienced a similar effect, and the two Danes came to realize the nasty interaction between alcohol and disulfiram. They decided to shift their research focus and explore the use of this drug in the treatment of alcohol dependence.
A second alcohol-ruining substance is cyanamide. Closely resembling hydrogen cyanide but not quite as bad for your health, it's used by pharmaceutical companies to synthesize certain drugs (e.g. cimetidine). It's also used in agriculture as a fertilizer (it contains easily accessible nitrogen) and a growth regulator (it's sprayed on peach trees and grapevines early on in the growing season to ensure they start sending out shoots from their buds at the same time).
|Effect of hydrogen cyanamide (HC) on budbreak in kiwifruit (Source)|
In 1914, a German physician by the name of Franz Koelsch reported an acute illness he had observed among people working with cyanamide. Their faces would flush bright red ("mal rouge"), they'd have a headache and feel lightheaded, their hearts would beat faster, and they'd have trouble breathing regularly. Koelsch discovered the illness, which usually lasted an hour or two before transforming into sleepiness, only occurred if the workers had recently consumed alcohol, even if it was just a single pint.
While not as popular as disulfiram, at least in the USA, cyanamide and derivatives of this compound have seen use in the treatment of alcohol dependence in many parts of the world. For example, calcium carbimide (trade name Temposil) is a mixture of methylcyanamide and calcium 2-hydroxypropane-1,2,3-tricarboxylate. It was developed in the years following WWII by Gordon Bell and Ken Ferguson, two Canadian researchers with a shared interest in addiction medicine. Bell, a physician, had previously treated patients with disulfiram, but wanted to find another drug with less intense side effects. After coming up with a promising candidate, the duo tested it out on themselves after consuming martinis. I can only imagine how weird it must have felt to take something knowing it would make you feel gross yet being excited for that very reason.
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