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Robert Samples Mr. Caste 1/1/10 Pre-AP Chemistry Chemical Research Paper: Ergolines

Lysergic acid and its various derivatives have been very influential in the course of history and most likely in the lives of many people that would be found shopping at a big box store. Lysergic acid derivatives are used for a wide array of applications in various medical fields. The 1-methyl 1-hydroxybutyl amide variant Is used to constrict the swollen blood vessels in the brains of chronic migraine sufferers to relieve pain. Whereas the 1hydroxybutyl amide version is used to induce labor in pregnant women and strengthen uterine contractions, reducing time in labor and damage to the fetus due to decreased circulation dramatically, As well as reducing post-natal bleeding. Lysergamide research is still alive and well today. There have been complex salts discovered that are being tested on dementia and Parkinson's patients and may even improve active memory in adults as well as the elderly! (Online Drug Information Center) Lysergic acid and its related compounds have also had a significant impact on history. A mixture of Lysergamides present in Claviceps purpurea (ergot) fungus are responsible for the condition know as egotism or colloidally “St. Anthony's Fire�. The fungus infects grains, particularly rye and even a small amount of infected material can contaminate a comparatively large amount of edible grain. Ergot alkaloids constrict the blood vessels by an unknown mechanism causing tissue necrosis, While possessing neurotoxic properties resulting in convulsions, delirium, and neurotic behavior. (Wong) In an outbreak of ergotism in dark age France during the 9 th century the vikings


overtook the coastal area of France while native opposition was weak. The region was only won back by the Holy Roman Empire after many years of raids and after the invaders had been assimilated into local culture. The area was never very secure from that point on, raids into the south continued and contributed to the break of the empire, And the establishing the modern day Franco-Germanic border that is still in use today. (Wong)

It has been proposed that ergotism is to blame for the atrocities of the Salem witch trials. In 1692 teen-aged girls exhibited strange symptoms similar to ergotism, these were perceived by the local population to be signs of witchcraft. In the indecent several people were executed on the charges of witchcraft. Ergotism may be to blame for this event. Infected bread was reported by some settler's journals. It could be possible that because of their developing brains, teenagers, perhaps especially girls exhibited a higher rate of psychosis due to low levels of ergot in communal grain. Whereas the rest of the population might have only suffered from subtle effects such as paranoia and hysteria, which may have further contributed the events. This cannot be proven, And many other theories exist, but it presents a compelling argument. (Wong) (PBS) The most widely known historical phenomenon in which lysergamides were involved needs no introduction, The acid craze of the 60's. Lysergic Acid Diethylamide is one of the most potent psychotropic substances known to man, possessing a threshold dose of only 20 ug; About 500-750 times as potent as a cousin class of psychoactive compounds, the Tryptamines. (erowid.org) It should be noted that the lethal dose of LSD has not been determined. Although in Kentucky several individuals intravenously injected approximately 1/3 of a gram of pure LSD, (more than 30,000 times the average recreational dose) mistaken for another substance. The individual suffered from nosebleeds and vivid hallucinations, But recovered after several hours under sedatives with no apparent ill effects. (Journal of the


Kentucky Medical Association) LSD was first synthesized by Albert Hoffman in 1938 but was forgotten until the early 50's when research into the compound resumed, starting with the CIA investigating it as a “truth serum” and later as an experimental drug for use in psychiatry. Eventually the drug hit the streets in the late 60's and was banned. Usage spiked In 1969 and was most prominent among the “Hippy” movement. This subculture was significant in influencing the political and social culture of the time, promoting the retreat from Vietnam, Shaping music and sexual norms for years to come, And birthing individuals as significant to history as Timothy Leary. (Hoffman) Ergoline Chemistry is a varied subject and can bridge many concepts in organic chemistry. There are only two know groups of natural sources of Ergoline and Lysergamide chemicals; Ergot fungus, And various woody vines related to the Morning glory, a common garden flower which contain primarily Ergine and its stereo-isomers. Ergine is known to be psychoactive and was used by the natives in Oaxaca, Mexico in religious ceremonies. (Steiner) Lysergamides (ergoline with an amide group at the 8 position and the 9/10 position being a double bond) Are very sensitive to light, heat, halogen gases and low Ph. The 8 position carbon will readily lose an electron in the presence of a moderately strong base, when this structure is restored to its uncharged state the hydrogen may approach from either side of the carbon, leading to a racemic mixture. The 9/10 double bond is very sensitive and any electrophile will attack and add to it, in the presence of light even water will attack the pi bond. (Shulgin) This presents an interesting problem to the chemist or company trying to work with such Lysergic acid compounds as halogenated compounds cannot be used, these are the most common leaving groups in organic synthesis, another issue is that these compounds may only be exposed to red light, which does not as readily break down the double bond. Perhaps the largest obstacles is their sensitivity to heat, preventing warm refluxes from being used, further slowing down reaction rate. (Shulgin) It should be considered quite a feat that


these compounds can be stored for any length of time as medications, let alone synthesized in under-equipped clandestine laboratories. Any synthesis must use activating agents. (Shulgin) Receptor affinities in the brain are very varied leading to unforeseen effects and a wide range of actions, lysergamide have been shown to selectively stimulate serotonin receptors in one part of the brain but depress activity of the same receptor in a different area. (Nichols)

Ergolines Produce such a wide variety of effects and reactions. Less than a 10 percent change in structure will change a toxin to a hallucinogen, A hallucinogen to a migraine medication, A migraine medication to tomorrow's next miracle drug. The legal waters for all these amazing possibilities are murky. The federal analogues act makes chemicals that bear a “resemblance� to scheduled compounds Illegal. This essentially allows the government and DEA to prosecute anyone producing a chemical that bears even a passing resemblance to an illicit drug. As of yet this has been used based upon primarily intent, unless the intent is for abuse legal action is not pursued. But this is a slippery slope, If someone in the DEA had a bone to pick with an R&D or pharmaceutical company what could happen to research on a potentially life saving drug? The Analogues Act is ambiguous and could easily be abused, It stunts research into an amazing field of pharmaceuticals and gives researchers a reason to worry if they are going to have their doors kicked in while they sleep. Ergoline compounds have been influential in practically everyones lives in complex ways. Anyone who had a birth in the last 20 years in a hospital (unless by Cesarean section) has been administered lysergamides in order to shorten labor from days to hours or minutes. The most effective migraine medications are based upon Lysergamides. Ergolines have influenced history in many ways, perhaps without them face of Europe would be different, or maybe Salem Massachusetts would have grown to be bigger than Boston, Could it also be


possible that without LSD influencing politics during the late 60's that the Vietnam war could have escalated and set off a nuclear holocaust between the United States and the Soviet Union? Perhaps everything would be the same without these chemicals, But it is possible, if not probable that that anonymous couple that met at Woodstock, whose great grandchild will cure cancer or start World War III, would not have met if it were not for a seemingly unimportant family of molecules.


Albert, Hoffman. My Problem Child. 1st. 1. New York: 1980. Print.

"methysergide", "Methergine", "Ergoloid", “Bromocriptine” Digitized PDR Consumer Drug Information Database. Online Drug Information Center, Web. <HTTP://www.drugs.com/cons/***.HTML>.

Wong, George. "Ergot of Rye: History." University of Hawaii. University of Hawaii, Web. 1 Jan 2010. <HTTP://www.botany.hawaii.edu/faculty/wong/BOT135 /LECT12.HTM>.

"Secrets of the Dead the Witches Curse." PBS. 2002. PBS, Web. 1 Jan 2010. <http://www.pbs.org/wnet/secrets /previous_seasons/case_salem/index.html>.

"LSD Dosage." Erowid Psychoactive Database. Erowid.org, 2009. Web. <http://www.erowid.org/chemicals /lsd/lsd_dose.shtml>.


Nichols, David. "Psychotropics." Pharmacology & Therapeutics 101. 2004. Print.

Griggs, Allen, and Ward, Micheal. "LSD Toxicity: A Suspected Cause of Death." Journal of the Kentucky Medical Association. (1977): Print. Shulgin, Alexander. TIKAL. Berkley: Transform Press, 1997. Print.

Steiner, . "Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae)." (2006): 533-544. Web. 2 Jan 2010. <http://www.ncbi.nlm.nih.gov/pubmed/16525783>.


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