Coprine

Symptoms

Symptoms of coprine poisoning include facial reddening/flushing, nausea, vomiting, malaise, agitation, palpitations, tingling in limbs, and sometimes headache and excessive salivation. This can be described as the alcohol flush reaction. Symptoms typically arise five to ten minutes after consumption of alcohol. If no more alcohol is consumed, the symptoms will generally subside over two to three hours, and symptom severity is proportional to the amount of alcohol consumed. Consumption of alcohol can induce these symptoms for up to 5 days after ingesting coprine. Interestingly, symptoms of coprine poisoning do not appear when the mushroom is ingested raw, but only when the mushroom is cooked.

In examining coprine poisoning cases in Germany in 2010, none of the patients died, and all made full recoveries after abstaining from alcohol. In one case medical care was not sought at all, and while there was a range in time of ethanol consumption after mushroom consumption, all the cases had well-cooked the mushrooms before ingestion.

The symptoms of coprine poisoning and alcohol consumption are similar to those induced by disulfiram (marketed as Antabuse), a drug utilized to treat chronic alcoholism by inducing severe side-effects to alcohol consumption. Because of this, research was done into the use of coprine as a similar drug for alcoholism. However, testing has shown coprine to have long-term mutagenic and reproductive effects, making it ill-suited for long-term use.

Mechanism of action

Coprine hydrolyzes to glutamic acid and 1-aminocyclopropanol, which inhibits the enzyme aldehyde dehydrogenase. 1-aminocyclopropanol quickly converts to cyclopropanone hydrate, which binds covalently to the thiol group present in the enzyme, deactivating the dehydrogenase activity. This inhibition then causes a buildup of acetaldehyde if ethanol is ingested. Since acetaldehyde is toxic and can no longer be metabolized to the less toxic acetic acid, the characteristic symptoms of coprine poisoning occur. However, as shown in the mechanism below, the covalent bonding is reversible, which is what allows symptoms to subside if no more alcohol is consumed.

1-Aminocyclopropanol also deactivates the esterase activity of aldehyde dehydrogenase, but less significantly.

Synthesis

Coprine is the first discovered compound with a naturally occurring cyclopropane group. Chemical synthesis can be effectively carried out by conducting an N-acylation reaction on 1-aminocyclopropanol. Treatment of isocyanatocyclopropane with hydrochloric acid leads to the hydrochloride of 1-aminocyclopropanol. Adding sodium hydroxide to create 1-aminocyclopropanol will destabilize the structure, so synthesis must be conducted using the hydrochloride. The addition of the hydrochloride to N-phthaloyl-L-glutamic anhydride will undergo acylation. Lastly, the blocking group is removed using hydrazine, yielding coprine. The enantiomer, isocoprine, is formed in negligible quantities in small-scale synthesis but is synthesized in higher amounts in large-scale, industrial synthesis.