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.[1] The toxins are also known as andromedotoxin, acetylandromedol, or rhodotoxin.

Contents

Chemical structure

Grayantoxin R1 R2 R3
Grayantoxin I OH CH3 H
Grayantoxin II CH2 H
Grayantoxin III OH CH3 Ac
Grayantoxin 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.[2] The grayanotoxin prevents inactivation, leaving excitable cells depolarized.

Poisoning

Honey from Japan, Brazil, United States, Nepal, and British Columbia is most likely to be contaminated with grayanotoxins, although very rarely to toxic levels. Historically the poisoning was associated with Rhododendron luteum and Rhododendron ponticum 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.[3]

Gross physical symptoms 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, 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.

In popular culture

The toxin from "hydrated rhododendron" is used in the 2009 film Sherlock Holmes to induce an "apparently mortal paralysis" in the movie's chief antagonist, Lord Blackwood.

References

  1. ^ Demircan, A; Keleş, A; Bildik, F; Aygencel, G; Doğan, NO; Gómez, HF (2009). "Mad honey sex: Therapeutic misadventures from an ancient biological weapon". Annals of emergency medicine 54 (6): 824–9. doi:10.1016/j.annemergmed.2009.06.010. PMID 19683834. 
  2. ^ Ito, S; Nakazato, Y; Ohga, A (1981). "Further evidence for the involvement of Na+ channels in the release of adrenal catecholamine: The effect of scorpion venom and grayanotoxin I". British journal of pharmacology 72 (1): 61–7. PMC 2071538. PMID 6261866. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2071538. 
  3. ^ Pliny the Elder on Mad Honey