Muscarine

Historically enormous and clinically small. Muscarine defined a receptor family and then contributed almost nothing else; it is a reference standard in the laboratory and a hazard in the woods. The single most useful thing to know about it is negative: it is not what makes fly agaric psychoactive, and repeating that it is has probably sent more people looking for the wrong antidote than any other error in popular mycology.

Muscarine poisoning is the cholinergic toxidrome with everything central subtracted. Onset is typically 15 minutes to 2 hours after the meal, and the picture is unopposed parasympathetic drive: sweating, salivation, lacrimation, miosis, blurred vision, abdominal pain, vomiting and diarrhoea, bradycardia or tachycardia, hypotension and syncope, with bronchial secretion and bronchoconstriction in heavier exposures ^[1]. Because muscarine acts only at muscarinic receptors and does not enter the brain, atropine is a true antidote rather than a partial one, unlike its role in organophosphate poisoning where the nicotinic and central components remain.

In a case series of 14 patients with mycologically confirmed Inocybe ingestion, supportive care with intravenous fluids, antiemetics and 1 mg of intravenous atropine produced full recovery within 12 hours in every case ^[1]. Severe outcomes including circulatory collapse are described, and a 2024 study complicates dose estimation: Clitocybe rivulosa and two fibre cap species store much of their muscarine as 4'-phosphomuscarine, a phosphorylated form with only weak affinity for the M3 receptor that unspecific esterase cleavage releases as free toxin, so the free muscarine measured in an intact mushroom can understate what a poisoned person actually receives ^[5].

Muscarine was isolated from Amanita muscaria in the nineteenth century and gave its name both to the receptor class it activates and, by extension, to the muscarinic versus nicotinic division that still organises cholinergic pharmacology. The irony is that the mushroom it is named after barely contains it. English-language mycology has for decades repeated a 1950s figure of 0.0003 percent muscarine in fresh fly agaric; a 2025 HPLC-MS/MS analysis found a range of 0.004 to 0.043 percent, higher than the consensus but still low ^[2].

The mushrooms that actually poison people with muscarine are elsewhere: a confirmed Inocybe serotina poisoning in Ningxia measured 324 mg of muscarine per kilogram of mushroom ^[7], and newly described tropical species in the Inocybaceae have been measured in grams per kilogram ^[8], a concentration fly agaric does not reach. Surveys across the Inocybaceae show muscarine is not a single ancestral trait but arose independently several times within the family ^[6].

Known to pharmacologists as an eponym, to emergency physicians as a toxidrome, and to almost nobody as a drug. It is also the subject of one of the most durable errors in popular writing about mushrooms, the assumption that muscarine is what makes fly agaric psychoactive; that mistake matters clinically, because it points toward atropine in a poisoning where atropine is the wrong answer and toward reassurance in the Inocybe poisonings where it is the right one.