Hemlock, poison from

Reynolds, T. 2005. Hemlock alkaloids from Socrates to poison aloes. Phytochemistry, 66 1399-1406. 

Langley first studied the action of drugs on the autonomic ganglia with the alkaloid nictoine obtained from Nicotiana tabacum. Subsequently, some other alkaloids were also foimd to possess similar effects, namely coniine from the poison Hemlock obtained from Conicum maculatum, gelsemine from the yellow jasmine and lobeline from the lobelia, a native of America. 

Reynolds T (2005) Hemlock Alkaloids from Socrates to Poison Aloes. Phytochemistry 66 1399... 

Brooks DE (2001) Plant poisoning, hemlock. Available from www.emedicine.com/emerg/ topic875.htm... 

Coniine is a neurotoxin of which less than 200 mg is fatal to humans. It can be isolated from poison hemlock and from the yellow pitcher plant. In the body, it causes paralysis by blocking the nicotinic receptors on the post-synaptic membrane of the neuromuscular junction. It does not affect the central nervous system therefore, the poisoned remains conscious until paralysis results in cessation of respiration. The first total synthesis was published by Ladenburg in 1886, in which he evenmaUy separated racemic coniine by classic resolution with tartaric acid. Historically, it became famous being the poison used to kill Socrates. 

Coniine (12), impHcated by Plato in the death of Socrates, is the major toxic constituent of Conium maculatum L. (poison hemlock) and, as pointed out eadier, was apparendy the first alkaloid to be synthesized. For years it was thought that coniine was derived from lysine (24), as were many of its obvious relatives containing reduced piperidine nuclei and a side chain, eg, peUetierine (46). However, it is now known (99) that coniine is derived from a polyketooctanoic acid [7028-40-2] (138), CgH QO, or some other similar straight chain analogue. 

Natural products that contain caibon-caibon triple bonds aie numerous. Two examples aie tariric acid, from the seed fat of a Guatemalan plant, and cicutoxin, a poisonous substance isolated from water hemlock. 

In ancient times, poison-hemlock seed was collected green, dried and stored to be used medicinally as a sedative. The dried leaf and juice of Conium maculatum L. (Hemlock) were listed in pharmacopoeias of London and Edinburgh from 1864 to 1898, and the last official record appeared in Great Britain in the British Pharmaceutical Codex of 1934. Interest in the medicinal value of poison-hemlock has declined because of the unpredictability of its effects. The unpredictability is now understood, the toxin profile and concentration in the plant and green seed can vary dramatically because of environmental factors or, even, diurnally. 

Figure 2.2 Three piperidine alkaloid teratogens from Conium maculatum (poison-hemlock) (a) coniine, (b) y-coniceine, and (c) A-methyl coniine, with accompanying LD50 as determined in a mouse bioassay.

In addition to lupines, poison-hemlock and Nicotiana spp., other plant species of the genera Genista, Prosopis, Lobelia, Cytisus, Sophora, Pinus, Punica, Duboisia, Sedum, Withania, Carica, Hydrangea, Dichroa, Cassia, Ammondendron, Liparia, and Colidium contain potentially toxic and teratogenic piperidine alkaloids. Many plant species or varieties from these genera may be included in animal and human diets (Keeler and Crowe, 1984). 

SOURCE - Extracted from Poisonous Hemlock (conium maculataum). 

Heterocycles which are not biosynthesized in humans, but which are natural products produced by other life forms, are very important in the history of drug design. This is particularly true of alkaloids containing a piperidine ring. These include coniine (8.87, extracted from poison hemlock, Conium maculatum, a member of the Umbelliferae carrot family), atropine (from Atropa belladonna and other genera of the Solanaceae plant family the plant was called belladonna [ beautiful woman ] since it was used by... 

The data shown in Table 2 illustrate the general paucity of comparative toxicity data within an isosteric series of chemicals. In this Table a variety of toxic end-points observed for benzene and naphthalene have been compared with those of their simple heterocyclic analogues, and it is clear that it is almost impossible to derive chemical structure-biological activity relationships from the published literature for even such a simple series of compounds. Even basic estimates of mammalian toxicity such as LD50 values cannot be accurately compared due either to the absence of relevant data or the noncomparability of those available. Thus in a field where there are little comparative data on the relative toxicity to mammals of pyrrole, thiophene and furan for example, it is difficult to relate chemical structure to biological activity in historical heterocyclic poisons such as strychnine (3) and hemlock [active agent coniine (4)]. 

Coniine, a toxic substance isolated from poison hemlock, contains only carbon, hydrogen, and nitrogen. Combustion analysis of a 5.024 mg sample yields 13.90 mg of C02 and 6.048 mg of H20. What is the empirical formula of coniine ... 

The simple piperidine alkaloid coniine from poison hemlock is not derived from lysine, but originates by an animation process and is discussed on page 381. 

Alkaloids are widespread in plants and include some very well-known poisons (notably coniine and strychnine), hallucinogens (morphine, cocaine and muscimol) and other potentially lethal compounds that are nevertheless used in medical practice (e.g. atropine, codeine, colchicine and morphine). As indicated by the preliminary snap-shot above, alkaloids typically have names ending in -ine and which are often related to the plant source or properties. Thus, morphine was named after Morpheus (the God of sleep) and coniine derives from Conium maculatum (hemlock), the plant used in the judicial murder of Socrates (399 BC). Various chemical tests for alkaloids are used as preliminary indicators of alkaloid presence in crude plant extracts. Finally, it should be noted that alkaloids can also exist as jVoxides of the alkaloid base. 

The natives of Peril were learning to ease their physical pains by chewing the leaves of coca shrub (Erytbroxylon tmxillence, "Rushy), which contain, among others, the alkaloid cocaine (11), and European citizens were recognizing other poisons such as coniine (12), from die poison hemlock ( Comum maculatum... 

The word toxicology is derived from the Greek words toxikon (arrow poison) and toxikos (the bow). Poisons were known about and used in warfare from the earliest times. However, there were other reasons for interest in poisons, and study of them had begun by 1500 bc. The Ebers Papyrus, the earhest medical records, include references to and recipes for poisons. Many of these are recognizable, such as hemlock, the plant toxin that the Greeks used for the execution of Socrates in 399 bc. Other substances listed are aconite, which was used as an arrow poison by the Chinese, and poisonous metals such as lead and antimony. Opium, which was used for both poisonous and beneficial purposes, has been known for at least 5,000 years. 

Apart from their documented use thoughout history poisons were also mentioned in literature, for example in Shakespeare s Macbeth Double, double toil and trouble . . . Root of hemlock, digg d i th dark. . In Flaubert s Madame Bovary, the victim was famously poisoned by arsenic, and arsenic again featured in the poem Under Milk Wood, by Dylan Thomas, in which arsenic biscuits were mentioned. 

Using the principles of VSEPR theory, you can predict the geometry around any atom in any molecule, no matter how complex. Enanthotoxin is a poisonous compound isolated from a common variety of hemlock grown in England. Predict the geometry around the indicated atoms in enanthotoxin. 

Coniine, a poisonous alkaloid isolated from the seeds, leaves, and roots of hemlock Conium maculatum), has been known since ancient times. Ingestion causes weakness, paralysis, and finally death. The Greek philosopher Socrates was executed by being forced to drink a potion prepared from hemlock in 339 b.c. 

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