Grayanotoxin

[5][6] Grayanotoxins are produced by plants in the family Ericaceae, specifically members of the genera Agarista, Craibiodendron, Kalmia, Leucothoe, Lyonia, Pieris and Rhododendron.

[3][7] The genus Rhododendron alone encompasses over 750 species that grow around the world in parts of Europe, North America, Japan, Nepal and Turkey.

Species with high concentrations of grayanotoxins, such as R. ponticum and R. luteum, are most commonly found in regions of Turkey bordering the Black Sea, and in Nepal.

Grayanotoxins can also be found in secondary plant products, such as honey, labrador tea, cigarettes, and herbal medicines.

[3] The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels located in the cell membrane of neurons.

[8] Experiments using squid axonal membranes indicate that sodium channel binding likely occurs on the internal face of the neuron.

This activated conformation allows for an influx of sodium ions resulting in cell depolarization, followed by the firing of an action potential.

When grayanotoxin is present, binding induces further conformational changes that prevent sodium channel inactivation and lead to a prolonged depolarization.

Owing to its transient ability to activate channels and increase membrane permeability to sodium ions, grayanotoxin is classified as a reversible Nav1.x agonist.

In higher doses, symptoms can include loss of coordination, severe and progressive muscular weakness, electrocardiographic changes of bundle branch block or ST-segment elevations as seen in ischemic myocardial threat, and nodal rhythm or Wolff-Parkinson-White syndrome.

[11] In addition to correcting rhythm disorders, administration of fluids and vasopressors can also help treat hypotension and mitigate other symptoms.

[22] According to Xenophon's Anabasis, an invading Greek army was accidentally poisoned by harvesting and eating the local Asia Minor honey, but they all made a quick recovery without any fatalities.

[24] The Roman soldiers became delirious and nauseated after being tricked into eating the toxic honey, at which point Mithridates' army attacked.