Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine.

The fly agaric mushroom contains four hallucinogens: muscarine, muscimol, muscazone, and ibotenic acid. In 1912, Henry Dale hypothesized that muscarine or a similar substance was the neurotransmitter at parasympathetic nerve endings, but he and Otto Loewi later isolated the actual transmitter and showed it was acetylcholine, not muscarine. The receptor is now called cholinergic or muscarinic. This discovery led to valuable drugs: pilocarpine for glaucoma and ipratropium for lung diseases.

Study at a glance

Abstract

The mushroom Amanita muscaria (fly agaric) is widely distributed throughout continental Europe and the UK. Its common name suggests that it had been used to kill flies, until superseded by arsenic. The bioactive compounds occurring in the mushroom remained a mystery for long periods of time, but eventually four hallucinogens were isolated from the fungus: muscarine, muscimol, muscazone and ibotenic acid. The shamans of Eastern Siberia used the mushroom as an inebriant and a hallucinogen. In 1912, Henry Dale suggested that muscarine (or a closely related substance) was the transmitter at the parasympathetic nerve endings, where it would produce lacrimation, salivation, sweating, bronchoconstriction and increased intestinal motility. He and Otto Loewi eventually isolated the transmitter and showed that it was not muscarine but acetylcholine. The receptor is now known variously as cholinergic or muscarinic. From this basic knowledge, drugs such as pilocarpine (cholinergic) and ipratropium (anticholinergic) have been shown to be of value in glaucoma and diseases of the lungs, respectively.