Oenanthotoxin is a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...

extracted from hemlock water-dropwort ('' Oenanthe crocata'') and other plants of the genus '' Oenanthe''. It is a central nervous system poison, and acts as a

noncompetitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

of the

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

gamma-aminobutyric acid. 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, polyyne, ...

and

carotatoxin Falcarinol (also known as carotatoxin or panaxynol) is a natural pesticide and fatty alcohol found in carrots (''Daucus carota''), red ginseng (''Panax ginseng'') and ivy. In carrots, it occurs in a concentration of approximately 2 mg/kg. A ...

. 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 Greek philosopher from Athens who is credited as the founder of Western philosophy and among the first moral philosophers of the ethical tradition of thought. An enigmatic figure, Socrates authored no t ...

and

Homer Homer (; grc, Ὅμηρος , ''Hómēros'') (born ) was a 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. Homer is considered one of the ...

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'', 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-like properties in small amounts.

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 Polyacetylene (IUPAC name: polyethyne) usually refers to an organic polymer with the repeating unit . The name refers to its conceptual construction from polymerization of acetylene to give a chain with repeating olefin groups. This compound ...

that act as noncompetitive gamma-aminobutyric acid (GABA) inhibitors in the

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

(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 GABA. For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic neuron produces GABA. A ...

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

Symptoms

While 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 dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs. Normally, a ...

rhabdomyolysis Rhabdomyolysis (also called 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 of ...

, renal failure, respiratory impairment, and cardiac dysrhythmias. Below is a comprehensive table listing the recorded symptoms caused 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