Hemlock Toxin

1. Hemlock Toxin Gregory N. Ortiz Biology 445 May 4, 2007

2. Topics • Hemlock – The Plant • Description • Location • Chemical Composition • Biochemical Properties of Toxin • Nicotinic-Acetylcholine Channel • Effects of Toxin • Medicinal Properties • Can it be used as a treatment? • Hemlock in History • Fate of Socrates Drawing courtesy of USDA (http://plants.usda.gov/java/profile?symbol=COMA2)

3. Hemlock – The Plant Photos courtesy of USDA (http://plants.usda.gov/java/profile?symbol=COMA2)

4. Description of Hemlock • By far the most familiar species is Conium maculatum - the most common of several species of hemlock characterized by their toxicity. • It is a herbaceous biennial plant which grows between 1.5-2.5 m tall, with a smooth green stem, usually spotted or streaked with red or purple on the lower half of the stem. • The leaves are finely divided and lacy, overall triangular in shape, up to 50 cm long and 40 cm broad. The flowers are small, white, clustered in umbels up to 10-15 cm across. • The plant is often mistaken for fennel, parsley or wild carrot although the characteristic stem hairs of the wild carrots are missing. The Conium root is fleshy, white and often unbranched and can be mistaken for parsnip.

5. Poison Hemlock Classified

6. More Hemlock Info. • A useful trick to determine whether a plant is poison hemlock rather than fennel (which it resembles) is to crush some leaves and smell the result. Fennel smells like liquorice, but poison hemlock smells “mouse-like” or musty. Discard it if you can’t tell the difference. • Poison hemlock flourishes in the spring, when most other forage is gone. All parts of the plant are poisonous but once the plant is dried the poison is greatly reduced (but not gone completely). • Hemlock goes by other names such as: "poison parsley" or "spotted parsley".

7. Distribution of Hemlock in U.S. Conium maculatum has been introduced and naturalized in many other areas, including much of Asia, N. America and Australia. Poison hemlock is often found on poorly drained soils, particularly near streams, ditches, and other surface water. Map courtesy of USDA (http://plants.usda.gov/java/profile?symbol=COMA2)

8. Chemical Composition • Hemlock contains the following alkaloids: • Coniine • N-methylconiine • Conhydrine • Pseudoconhydrine • g-coniceïne • Atropine The most important and toxic of these is Coniine. Coniine is a neurotoxin, which disrupts the workings of the central nervous system (CNS). Picture courtesy of Wikipedia

9. Biochemical Properties • There are two main classes of acetylcholine receptor (AChR), nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). They are named for the ligands used to discover the receptors. • Nicotinic AChRs are ionotropic receptors permeable to sodium, potassium, and chloride ions. They are stimulated by nicotine (low concentrations) and acetylcholine and blocked by nicotine (high concentrations) and hemlock toxin. • Nicotinic acetylcholine receptors are present in many tissues in the body. The neuronal receptors are found in the central nervous system and the peripheral nervous system. The neuromuscular receptors are found in the neuromuscular junctions of somatic muscles; stimulation of these receptors causes muscular contraction.

10. Acetylcholine and its Receptor Acetylcholine Receptor (nAChR) Acetylcholine (Ach) Pictures courtesy of Wikipedia

11. Effect of Toxin • Hemlock toxin funtions by binding to the post-synaptic cell receptor of the of the target cell (#4) • This results in decreased transmitter (#3) biding, which causes CNS and muscle cell inhibition and eventual cessation of cell signaling (boxes with X’s) Diagram courtesy of Wikipedia

12. Toxin bound to Receptor Picture courtesy of Wikipedia

13. Effects of Toxin • In poisonous/lethal doses: • it produces complete paralysis including loss of speech • respiration initially becomes depressed • respiration eventually ceases completely • death results from asphyxia • brain and the rational faculties remain unaffected and alert up to the time of death

14. Medicinal Properties • Treatment wasn't always effective as the difference between a therapeutic and a toxic amount is very slight. • Poison hemlock has been used as a sedative and for its antispasmodic properties. • Also used by Greek and Persian physicians for a variety of problems, such as arthritis. • As an inhalant it is said to relieve cough in bronchitis, whooping-cough, asthma, etc. • Hemlock juice (Succus conii) has been prescribed as a remedy in cases of undue nervous motor excitability, such as: • teething in children • epilepsy • spasms of the larynx and gullet • in acute mania

15. Hemlock in History "The man … laid his hands on him and after a while examined his feet and legs, then pinched his foot hard and asked if he felt it. He said ‘No’; then after that, his thighs; and passing upwards in this way he showed us that he was growing cold and rigid. And then again he touched him and said that when it reached his heart, he would be gone. The chill had now reached the region about the groin, and uncovering his face, which had been covered, he said – and these were his last words – 'Crito, we owe a cock to Asclepius. Pay it and do not neglect it.' 'That,' said Crito, 'shall be done; but see if you have anything else to say.' To this question he made no reply, but after a little while he moved; the attendant uncovered him; his eyes were fixed. And Crito when he saw it, closed his mouth and eyes." In ancient Greece, hemlock was used to poison condemned prisoners, with the most famous victim being the philosopher Socrates. After being condemned to death for impiety in 399 BC, Socrates was given a strong solution of the hemlock plant. Plato described Socrates' death in the “Phaedo”:

16. Socrates Death of Socrates Bust of Socrates Photos courtesy of Wikipedia

17. References • Assorted authors. 2003. State noxious weed lists for 46 states. State agriculture or natural resource departments. • Haragan, P.D. 1991. Weeds of Kentucky and adjacent states: a field guide. The University Press of Kentucky. Lexington, Kentucky. 278pp. • Plato, Phaedo 117e-118a, trans. Loeb Classical Library, Harvard University Press, Cambridge, Mass., 1990 edition, pp. 401-3. • Southeast Exotic Pest Plant Council. 1996. Invasive exotic pest plants in Tennessee (19 October 1999). Research Committee of the Tennessee Exotic Pest Plant Council. Tennessee. • United States Department of Agriculture (USDA) - Plants database. http://plants.usda.gov/java/profile?symbol=COMA2. • Uva, R.H., J.C. Neal, & J.M. DiTomaso. 1997. Weeds of the Northeast. Cornell University Press. Ithaca, New York. 397pp. • Whitson, T.D. (ed.) et al. 1996. Weeds of the West. Western Society of Weed Science in cooperation with Cooperative Extension Services, University of Wyoming. Laramie, Wyoming. 630pp. • Wikipedia. http://en.wikipedia.org/wiki/Main_Page.