Physostigmine
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Physostigmine
Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree. The chemical was synthesized for the first time in 1935 by Percy Lavon Julian and Josef Pikl. It is available in the U.S. under the trade names Antilirium and Isopto Eserine, and as eserine salicylate and eserine sulfate. Today, physostigmine is most commonly used for its medicinal value. However, before its discovery by Sir Robert Christison in 1846, it was much more prevalent as an ordeal poison. The positive medical applications of the drug were first suggested in the gold medal-winning final thesis of Thomas Richard Fraser at the University of Edinburgh in 1862. Medical uses Physostigmine is used to treat glaucoma and delayed gastric emptying. Because it enhances the transmission of acetylcholine s ...
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Calabar Bean
''Physostigma venenosum'', the Calabar bean or ordeal bean, is a leguminous plant, Endemic to tropical Africa, with a seed poisonous to humans. It derives the first part of its scientific name from a curious beak-like appendage at the end of the stigma, in the centre of the flower; this appendage, though solid, was supposed to be hollow (hence the name from , a bladder, and stigma). Growth The plant is a large, herbaceous, climbing perennial, with the stem woody at the base, up to in diameter; it has a habit like the scarlet runner, and attains a height of about . The flowers, appearing in axillary peduncles, are large, about long, grouped in pendulous, fascicled racemes pale-pink or purplish, and heavily veined. The seed pods, which contain two or three seeds or beans, are in length; and the beans are about the size of an ordinary horse bean but less flattened, with a deep chocolate-brown color. Toxicology Calabar bean contains physostigmine, a reversible cholinesterase i ...
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Percy Lavon Julian
Percy Lavon Julian (April 11, 1899 – April 19, 1975) was an American research chemist and a pioneer in the chemical synthesis of medicinal drugs from plants. He was the first to synthesize the natural product physostigmine and was a pioneer in the industrial large-scale chemical synthesis of the human hormones progesterone and testosterone from plant sterols such as stigmasterol and sitosterol. His work laid the foundation for the steroid drug industry's production of cortisone, other corticosteroids, and birth control pills. He later started his own company to synthesize steroid intermediates from the wild Mexican yam. His work helped greatly reduce the cost of steroid intermediates to large multinational pharmaceutical companies, helping to significantly expand the use of several important drugs, including synthesizing cortisone. He received more than 130 chemical patents. He was one of the first African Americans to receive a doctorate in chemistry. He was the first African- ...
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Eseroline
Eseroline is a drug which acts as an opioid agonist. It is a metabolite of the acetylcholinesterase inhibitor physostigmine but unlike physostigmine, the acetylcholinesterase inhibition produced by eseroline is weak and easily reversible, and it produces fairly potent analgesic effects mediated through the μ-opioid receptor. This mixture of activities gives eseroline an unusual pharmacological profile, although its uses are limited by side effects such as respiratory depression and neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall .... References Semisynthetic opioids Pyrroloindoles Phenols Mu-opioid receptor agonists {{analgesic-stub ...
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Anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, sweat glands, and many other parts of the body. In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central and peripheral nervous system and at the neuromuscular junction: antimuscarinic agents, and antinicotinic agents ( ganglionic blockers, neuromuscular blockers). The term "anticholinergic" is typically used to refer to antimuscarinics which competitively inhibit the binding of ACh to muscarinic acetylcholine receptors; such agen ...
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Atropa Belladonna
''Atropa belladonna'', commonly known as belladonna or deadly nightshade, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes, and eggplant (aubergine). It is native to Europe, North Africa, and Western Asia. Its distribution extends from Great Britain in the west to western Ukraine and the Iranian province of Gilan in the east. It is also naturalised or introduced in some parts of Canada and the United States. The foliage and berries are extremely toxic when ingested, containing tropane alkaloids. These toxins include atropine, scopolamine, and hyoscyamine, which cause delirium and hallucinations, and are also used as pharmaceutical anticholinergics. Tropane alkaloids are of common occurrence not only in the Old World tribes Hyoscyameae (to which the genus Atropa belongs) and Mandragoreae, but also in the New World tribe Datureae - all of which belong to the subfamily Solanoideae of the plant family Solanaceae. ...
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Robert Christison
Sir Robert Christison, 1st Baronet, (18 July 1797 – 27 January 1882) was a Scottish toxicologist and physician who served as president of the Royal College of Physicians of Edinburgh (1838–40 and 1846-8) and as president of the British Medical Association (1875). He was the first person to describe renal anaemia. Life Christison was born at 144 Nicolson Street in Edinburgh, the son of Margaret Johnstone and Alexander Christison FRSE (1753–1820). He was a twin, his elder brother (by a few minutes) being later Rev. Alexander Christison (1797–1874). He attended the Royal High School before studying medicine at University of Edinburgh, graduating in 1819. At this time the family were living at 4 Argyll Square. He then spent a short time in London, studying under John Abernethy and Sir William Lawrence, and in Paris, where he learned analytical chemistry from Pierre Robiquet and toxicology from Mathieu Orfila. In 1822 he returned to Edinburgh as professor of medical ...
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Manchineel Tree
The manchineel tree (''Hippomane mancinella'') is a species of flowering plant in the spurge family (Euphorbiaceae). Its native range stretches from tropical southern North America to northern South America. The name "manchineel" (sometimes spelled "''manchioneel''" or "''manchineal''"), as well as the specific epithet ''mancinella'', are from Spanish manzanilla ("little apple"), from the superficial resemblance of its fruit and leaves to those of an apple tree. It is also called beach apple. A present-day Spanish name is ', "little apple of death". This refers to the fact that manchineel is one of the most toxic trees in the world: the tree has milky-white sap which contains numerous toxins and can cause blistering. The sap is present in every part of the tree bark, leaves, and fruit.Dean, Signe (4 January 2016"The horrifying experience a radiologist had after eating fruit from the 'tree of death'" ''Business Insider'' Description ''Hippomane mancinella'' grows up to tall. ...
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Ordeal Poison
Trial by ordeal was an ancient judicial practice by which the guilt or innocence of the accused was determined by subjecting them to a painful, or at least an unpleasant, usually dangerous experience. In medieval Europe, like trial by combat, trial by ordeal, such as cruentation, was sometimes considered a "judgement of God" ( la, jūdicium Deī, ang, Godes dōm): a procedure based on the premise that God would help the innocent by performing a miracle on their behalf. The practice has much earlier roots, attested to as far back as the Code of Hammurabi and the Code of Ur-Nammu. In pre-modern society, the ordeal typically ranked along with the oath and witness accounts as the central means by which to reach a judicial verdict. Indeed, the term ''ordeal'', Old English ''ordǣl'', has the meaning of "judgment, verdict" (German ''Urteil'', Dutch ''oordeel''), from Proto-Germanic ''*uzdailiją'' "that which is dealt out". Priestly cooperation in trials by fire and water was forbidd ...
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Datura Stramonium
''Datura stramonium'', known by the common names thorn apple, jimsonweed (jimson weed), devil's snare, or devil's trumpet, is a poisonous flowering plant of the nightshade family Solanaceae. It is a species belonging to the ''Datura'' genus and '' Daturae'' tribe. Its likely origin was in Central America, and it has been introduced in many world regions. It is an aggressive invasive weed in temperate climates across the world. ''D. stramonium'' has frequently been employed in traditional medicine to treat a variety of ailments. It has also been used as a hallucinogen (of the anticholinergic/antimuscarinic, deliriant type), taken entheogenically to cause intense, sacred or occult visions.Schultes, Richard Evans; Albert Hofmann (1979). ''Plants of the Gods: Origins of Hallucinogenic Use'' New York: McGraw-Hill. . It is unlikely ever to become a major drug of abuse owing to effects upon both mind and body frequently perceived as being highly unpleasant, giving rise to a state of ...
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Dimenhydrinate
Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chlorotheophylline, a chlorinated theophylline derivative, in a 1:1 ratio. Medical uses Nausea Dimenhydrinate is an over-the-counter (OTC) antihistamine indicated for the prevention and relief of nausea and vomiting from a number of causes. It is an H1 receptor antagonist that demonstrates anticholinergic activity. Medicinal chemistry Diphenhydramine is the primary constituent of dimenhydrinate and dictates the primary effect. The main difference relative to pure diphenhydramine is a lower potency due to being combined with 8-chlorotheophylline. By weight, dimenhydrinate is between 53% to 55.5% diphenhydramine. Side effects Common side effects may include: *Drowsiness *Dry mouth, nose, or throat *Constipation *Blurred vision *Feeling restl ...
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Atropine
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings. Common side effects include a dry mouth, large pupils, urinary retention, constipation, and a fast heart rate. It should generally not be used in people with angle closure glaucoma. While there is no evidence that its use during pregnancy causes birth defects, that has not been well studied. It is likely safe during breastfeeding. It is an antimuscarinic (a type of anticholinergic) that works by inhibiting the parasympathetic nervous system. Atropine occurs n ...
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Gamma-Hydroxybutyrate
''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. It acts on the GHB receptor and is a weak agonist at the GABAB receptor. GHB has been used in the medical setting as a general anesthetic and as treatment for cataplexy, narcolepsy, and alcoholism. It is also used illegally as an intoxicant, as an athletic-performance enhancer, as a date-rape drug, and as a recreational drug. It is commonly used in the form of a salt, such as sodium γ-hydroxybutyrate (NaGHB, sodium oxybate, or Xyrem) or potassium γ-hydroxybutyrate (KGHB, potassium oxybate). GHB is also produced as a result of fermentation, and is found in small quantities in some beers and wines, beef, and small citrus fruits. Succinic semialdehyde dehydrogenase deficiency is a disease that causes GHB to accumulate in the blood. Medic ...
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