Grayanotoxin

Grayanotoxins are a group of closely related toxins found in rhododendrons and other plants of the family Ericaceae. They can be found in honey made from their nectar and cause a very rare poisonous reaction called grayanotoxin poisoning, honey intoxication, or rhododendron poisoning. Grayanotoxin I (see below) is also known as andromedotoxin, acetylandromedol, rhodotoxin and asebotoxin; the systematic chemical name is: grayanotaxane-3,5,6,10,14,16-hexol 14-acetate. Grayanotoxins are named after Leucothoe grayana, a plant species from Japan, which is in turn named after 19th century American botanist Asa Gray.

Chemical structure

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Grayanotoxin	R1	R2	R3
Grayanotoxin I	OH	CH3	Ac
Grayanotoxin II	CH2		H
Grayanotoxin III	OH	CH3	H
Grayanotoxin IV	CH2		Ac

Ac = acetyl

Grayanotoxins are polyhydroxylated cyclic diterpenes. They bind to specific sodium ion channels in cell membranes, the receptor sites involved in activation and inactivation. The grayanotoxin prevents inactivation, leaving excitable cells depolarized.

Poisoning

Poisoning from graynotoxins is rarely fatal in humans, but can be lethal for other animals. Physical symptoms from grayanotoxin poisoning occur after a dose-dependent latent period of minutes to three hours or so. Initial symptoms are excessive salivation, perspiration, vomiting, dizziness, weakness and paresthesia in the extremities and around the mouth, low blood pressure and sinus bradycardia. In higher doses symptoms can include loss of coordination, severe and progressive muscular weakness, electrocardiographic changes of bundle branch block and/or ST-segment elevations as seen in ischemic myocardial threat, bradycardia (and, paradoxically, ventricular tachycardia), and nodal rhythm or Wolff-Parkinson-White syndrome. Despite the potential cardiac problems the condition is rarely fatal and generally lasts less than a day. Medical intervention is not often needed but sometimes atropine therapy, vasopressors and other agents are used to mitigate symptoms.

Mad honey disease

File:Pontische rododendron struik (Rhododendron ponticum).jpg

Rhododendron ponticum

Grayanotoxins can be found in honey produced from the pollen of plants such as Rhododendron ponticum that contains alkaloids that are poisonous to humans. Such honey is called 'mad honey' Honey from Japan, Brazil, United States, Nepal, and British Columbia is most likely to be contaminated with grayanotoxins, although very rarely to toxic levels. In Nepal, this type of honey is used by the Gurung people both for its medicinal and hallucinogenic properties.

Honey produced from the nectar of Andromeda polifolia contains high enough levels of grayanotoxin to cause full body paralysis and potentially fatal breathing difficulties due to diaphragm paralysis. Honey obtained from spoonwood and allied species such as sheep-laurel can also cause illness. The honey from Lestrimelitta limao also produces this paralyzing effect seen in the honey of A. polifolia and is also toxic to humans.

There have been famous episodes of inebriation of humans from consuming toxic honey throughout history. Xenophon, Aristotle, Strabo, Pliny the Elder, and Columella all document the results of eating this "maddening" honey. Historically the toxin in the honey was derived from the pollen and nectar of Rhododendron luteum and Rhododendron ponticum, which are found around the Black Sea. According to Pliny and later Strabo, the locals used the honey against the armies of Xenophon in 401 BCE and later against Pompey in 69 BCE. When Roman troops under Pompey the Great attacked the Heptakometes in Turkey, and they were poisoned by the honey from honeycombs deliberately placed along their route. The Roman soldiers became delirious and nauseous after eating the toxic honey, leading to an easy defeat.

Honey containing grayanotoxin known as deli bal is still deliberately produced in the Caucasus region of Turkey. In the eighteenth century, this honey was exported to Europe to add to alcoholic drink to give it extra potency.