Coprine

The ink cap--Coprinus atramentarius (Bulliard ex Fries) Fries--is responsible for poisoning when ingested with alcohol. The investigation of the "Coprinus syndrome," although a minor poisoning incident, stimulated numerous research programs because the results were expected to yield a novel drug useful during the treatment of alcoholism. This work led to the identification of the active principle--coprine--and to an explanation of its mode of action; nevertheless, detailed toxicology investigations have shown that the mutagenic and gonadotoxic properties of this compound made it unsuitable for therapeutic use. Our current knowledge of the poisoning, the chemistry of the toxin, and its mode of action are here reviewed.

The effects of disulfiram and coprine on brain tryptophan hydroxylation, and on the brain-levels of serotonin and 5-hydroxyindole-3-acetic acid, were studied in 45 and 235 days old rats. Both drugs were found to affect the parameters measured. Disulfiram increased the rate of tryptophan hydroxylation and the serotonin level in young rats, while these parameters appeared to be unaffected in old disulfiram-treated rats. In contrast, coprine increased the rate of tryptophan hydroxylation and possibly also the serotonin level in old rats while no significant effects were seen in young coprine-treated rats. Regarding the 5-hydroxyindole-3-acetic acid concentration, this appeared to be increased by disulfiram in both age-groups, while no significant effects were found with coprine. The lack of similarity in the action of disulfiram and coprine, which are both potent aldehyde dehydrogenase inhibitors, suggests that the effects found were not caused by an impaired metabolism of monoamine-derived biogenic aldehydes.

Alcohol intolerance after consumption of wild mushrooms is a recognized phenomenon. This is best understood with Coprinus atramentarius. Its active component Coprine blocks enzymatic ethanol degradation at the stage of acetaldehyde, which is responsible for the well-recognized symptoms. Here, we report three events in five patients experiencing the same symptoms after consumption of self-collected Lepiota aspera. All had mistaken L. aspera for edible mushrooms as Amanita rubescens or Macrolepiota procera. In all events, L. aspera was identified by mycologists and no other mushrooms were involved. The mushrooms were well sautéed and tolerated well until an alcoholic beverage was consumed. Then within few minutes facial flushing, throbbing headache, tachycardia, and shortness of breath all occurred. The symptoms abated within a few hours with no sequelae but could be re-provoked by further alcohol consumption up to 48 h later. This syndrome appears to be identical with the one known from C. atramentarius. However, the toxin in L. aspera or its mechanism is not yet known.