Grayanotoxins are a group of closely related toxin

Toxin

A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

s found in rhododendron

Rhododendron

Rhododendron is a genus of over 1 000 species of woody plants in the heath family, most with showy flowers...

s and other plants of the family Ericaceae

Ericaceae

The Ericaceae, commonly known as the heath or heather family, is a group of mostly calcifuge flowering plants. The family is large, with roughly 4000 species spread across 126 genera, making it the 14th most speciose family of flowering plants...

. They can be found in honey

Honey

Honey is a sweet food made by bees using nectar from flowers. The variety produced by honey bees is the one most commonly referred to and is the type of honey collected by beekeepers and consumed by humans...

 made from their nectar and cause a very rare poisonous reaction called grayanotoxin poisoning, honey intoxication, or rhododendron poisoning. The toxins are also known as andromedotoxin, acetylandromedol, or rhodotoxin.

Grayanotoxins are polyhydroxylated cyclic diterpene

Terpene

Terpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are often strong smelling and thus may have had a protective...

. They bind to specific sodium ion channel

Sodium ion channel

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e...

s in cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

s, the receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 sites involved in activation and inactivation. The grayanotoxin prevents inactivation, leaving excitable cells depolarized.

Gross physical symptoms occur after a dose-dependent latent period of minutes to three hours or so. Initial symptoms are excessive salivation, perspiration, vomiting

Vomiting

Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, dizziness

Dizziness

Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....

, weakness

Weakness

Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise, dizziness, or fatigue. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a...

 and paresthesia

Paresthesia

Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...

 in the extremities and around the mouth, low blood pressure and sinus bradycardia

Sinus bradycardia

Sinus bradycardia is a heart rhythm that originates from the sinus node and has a rate of under 60 beats per minute.-Signs and symptoms:The decreased heart rate can cause a decreased cardiac output resulting in symptoms such as lightheadedness, dizziness, hypotension, vertigo, and syncope...

. In higher doses symptoms can include loss of coordination, severe and progressive muscular weakness, bradycardia

Bradycardia

Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

 (and, paradoxically, ventricular tachycardia

Ventricular tachycardia

Ventricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...

), and nodal rhythm or Wolff-Parkinson-White syndrome

Wolff-Parkinson-White syndrome

Wolff–Parkinson–White syndrome is a disorder of the heart in which the ventricles of the heart contract prematurely due to an accessory pathway known as the bundle of Kent. This accessory pathway is an abnormal electrical communication from the atria to the ventricles...

. 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

Atropine

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

 therapy, vasopressors and other agents are used to mitigate symptoms.

Honey from Japan

Japan

Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

, Brazil

Brazil

Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, Nepal

Nepal

Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

, and British Columbia

British Columbia

British Columbia is the westernmost of Canada's provinces and is known for its natural beauty, as reflected in its Latin motto, Splendor sine occasu . Its name was chosen by Queen Victoria in 1858...

 is most likely to be contaminated with grayanotoxins, although very rarely to toxic levels. Historically the poisoning was associated with Rhododendron luteum

Rhododendron luteum

Rhododendron luteum, Yellow Azalea or Honeysuckle Azalea is a species of Rhododendron native to southeastern Europe and southwest Asia. In Europe, it occurs from southern Poland and Austria south through the Balkans and east to southern Russia, and in Asia, east to the Caucasus.It is a shrub...

and Rhododendron ponticum

Rhododendron ponticum

Rhododendron ponticum, called Common Rhododendron or Pontic Rhododendron, is a species of Rhododendron native to southern Europe and southwest Asia.-Description:...

found around the Black Sea

Black Sea

The Black Sea is bounded by Europe, Anatolia and the Caucasus and is ultimately connected to the Atlantic Ocean via the Mediterranean and the Aegean seas and various straits. The Bosphorus strait connects it to the Sea of Marmara, and the strait of the Dardanelles connects that sea to the Aegean...

. According to Pliny

Pliny the Elder

Gaius Plinius Secundus , better known as Pliny the Elder, was a Roman author, naturalist, and natural philosopher, as well as naval and army commander of the early Roman Empire, and personal friend of the emperor Vespasian...

 and later Strabo

Strabo

Strabo, also written Strabon was a Greek historian, geographer and philosopher.-Life:Strabo was born to an affluent family from Amaseia in Pontus , a city which he said was situated the approximate equivalent of 75 km from the Black Sea...

 the locals used the honey against the armies of Xenophon

Xenophon

Xenophon , son of Gryllus, of the deme Erchia of Athens, also known as Xenophon of Athens, was a Greek historian, soldier, mercenary, philosopher and a contemporary and admirer of Socrates...

 in 401 BCE and later against Pompey

Pompey

Gnaeus Pompeius Magnus, also known as Pompey or Pompey the Great , was a military and political leader of the late Roman Republic...

 in 69 BCE.

The toxin is used in the 2009 film Sherlock Holmes

Sherlock Holmes (2009 film)

Sherlock Holmes is a 2009 action-mystery film based on the character of the same name created by Sir Arthur Conan Doyle. The film was directed by Guy Ritchie and produced by Joel Silver, Lionel Wigram, Susan Downey and Dan Lin. The screenplay by Michael Robert Johnson, Anthony Peckham and Simon...

(from 'hydrated Rhododendron') to induce an "apparently mortal paralysis" in Lord Blackwood.