Oenanthotoxin is a

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

extracted from hemlock water-dropwort (''

Oenanthe crocata ''Oenanthe crocata'', hemlock water-dropwort (sometimes known as dead man's fingers) is a flowering plant in the Apiaceae, carrot family, native to Europe, North Africa and western Asia. It grows in damp grassland and wet woodland, often along ri ...

'') and other plants of the genus '' Oenanthe''. It is a central nervous system poison, and acts as a noncompetitive antagonist of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

gamma-aminobutyric acid GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

. A case has been made for the presence of this toxin in local '' Oenanthe'' species playing a causative role in euthanasia in ancient Sardinia. It was crystallized in 1949 by Clarke and co-workers. It is structurally closely related to the toxins

cicutoxin Cicutoxin is a naturally-occurring poisonous chemical compound produced by several plants from the family Apiaceae including water hemlock ('' Cicuta'' species) and water dropwort (''Oenanthe crocata''). The compound contains polyene, polyyn ...

and carotatoxin. Oenanthotoxin is a C17 polyacetylene isomer of cicutoxin.

Occurrence

Oenanthotoxin concentration in plants is dependent on seasonal changes and geographical location, the most is present during late winter and early spring. Contrary to most poisonous plants that contain bitter tastes or burning sensations, the water dropwort has a rather sweet and pleasant taste and odor. Water dropwort is characterized by a yellow liquid that changes color due to air exposure. The roots are the most toxic part, although the entire plant contains poisonous properties.

History and culture

The discovery and use of plants containing oenanthotoxin predates

Socrates Socrates (; ; – 399 BC) was a Ancient Greek philosophy, Greek philosopher from Classical Athens, Athens who is credited as the founder of Western philosophy and as among the first moral philosophers of the Ethics, ethical tradition ...

and

Homer Homer (; , ; possibly born ) was an Ancient Greece, Ancient Greek poet who is credited as the author of the ''Iliad'' and the ''Odyssey'', two epic poems that are foundational works of ancient Greek literature. Despite doubts about his autho ...

and its first use as a poison is thought to have been implemented between 1800 BC and 800 BC in Pre-Roman Sardinia. In Ancient Sardinia, it was considered to be a humane form of euthanasia. Elderly people who were unable to care for themselves were given water dropwort and dropped from a high rock to ensure death. It is also believed that Socrates ingested the plant when executed. A common symptom of oenanthotoxin is ''

risus sardonicus ''Risus sardonicus'' or rictus grin is a highly characteristic, abnormal, sustained spasm of the facial muscles that appears to produce grinning. It may be caused by tetanus, strychnine poisoning, or Wilson's disease, and has been reported after ...

'', better known as the Sardonic Grin, coined by Homer in the 8th century BC, due to the victim's rigid smile after ingestion. Furthermore, as a muscle relaxant, it is believed to have cosmetic

botox Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endi ...

-like properties in small amounts. In fact a team of italian doctors and professors : Paolo Tramontano, Mauro Ballero, Armando Bianco, and Alessandro Venditti, in a cooperation with the researchers of the University of Rome “La Sapienza” and the University of Cagliari “uniCa” have discovered that this extract is capable of providing a tightening effect on the skin and preventing the formation of wrinkles by effectively and quickly combating mild and medium grade skin ptosis without resorting to invasive interventions and without side effects. The extracts are also effective in counteracting skin aging and re-establishing correct trophism. Studies showed that Oenanthotoxine and Dihydroenanthotoxin modulate muscle contraction, causing the blockade of the GABA receptors involved in the regulation of reflex contraction and motor neurons and determining the so-called "tensor effect" at the skin level. This extract has been patented and it is owned by Omegafarm S.R.L, Studio T Management S.R.L. and the University of Rome “La Sapienza”.

Mechanism of action

Although oenanthotoxin is a relatively well known poison, its mechanism of action is not entirely understood. However, there is evidence that its mechanism of action is similar to that of

. Oenanthotoxin is part of a group of C17 conjugated polyacetylenes that act as noncompetitive

(GABA) inhibitors in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS). GABA binds to the beta-domain of the GABA_A receptor in the central nervous system and activates the receptor increasing chloride ion flow across the membrane and inhibiting the neuron. When oenanthotoxin is introduced to the body, it non-competitively binds to the same beta-domain receptor as GABA and prevents normal inhibitory function. Binding to the same receptor, oenanthotoxin blocks the chloride channel, allowing excessive excitation to occur. This, blocking

GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...

responses, causes hyperactivity in the neurons, resulting in convulsions, and seizures.

Symptoms

Oenanthotoxin is extremely dangerous and toxic (LD₅₀ = 0.58 mg/kg for mice), there have been numerous case studies documenting the common symptoms including: convulsions, seizures, nausea, diarrhea,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

rhabdomyolysis Rhabdomyolysis (shortened as rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some o ...

, renal failure, respiratory impairment, and cardiac dysrhythmias. Below is a comprehensive table listing the recorded symptoms caused by oenanthotoxin within each system in the body ''Oenanthe crocata'':

References

{{Convulsants Neurotoxins Plant toxins Conjugated enynes Secondary alcohols Convulsants GABAA receptor negative allosteric modulators Conjugated diynes