Kathryn Klett Orgo Diekman

Morphine

Its amazing what a flower can do or rather, an unripe seed pod. Papaver somniferum has caused wars, addictions, and all sorts of governmental unrest, all because of the creamy exudate that sits on its seeds, quietly offering its subtle gift of peace and violence to men. It has grown for thousands of years the first written records of its dried exudate were taken by the Sumerians, 6000 years ago, and the Babylonians and Egyptians also wrote about its medical properties. Pliny the Elder wrote of the opium poppy in his works, and the Romans modeled the Greeks when they associated the flower with Somnus, their god of sleep. It is fitting then, that morphine, the most abundant alkaloid of opium, should be named for Morpheus, one of the Greek gods of sleep the Oneroi who brought dreams, rest, and sometimes death, with poppies in his hands. Incidentally, he also slept in a cave full of poppy seeds, and could bring
Morpheus The Opium Poppy

illusions and hallucinations with the help of his brothers, the other Oneroi. Much like Morpheus, morphine is a chemical that can be used for good or for

ill, and its path can be traced in wars and in medicines for as long as its parent plant has been around.

The Technical Stuff

Morphines chemical formula is C17H19NO3, and it makes up 914% of opiums constitution. Discovered in 1805 by an inexperienced but eager 21-year-old Friedrich Wilhelm Adam Sertrner (17831841), morphine remains the most widely used and powerful pain reliever in the medical practice. Oddly enough, it only dulls slow pain deep aches, not

the flash and burn of sudden pain. Morphine is made of three carbon rings, all lying on the same place, with two carbon rings jutting out at right angles from it. This structure is what allows morphine to bind to the active sites on neuron receptors, which stops pain signals from reaching the brain. For morphine to work, the single benzene fits neatly into a flat part of the receptor protein, while the carbon ring at an angle to the benzene goes into a groove right close by. This puts the nitrogen atom right next to a negatively charged group on the receptor, and since the nitrogen is positively charged (morphine is polar), the two molecules bind together, to bring almost-instant pain relief. Morphine is particularly effective because the receptor it binds to can be found in many of the neurons of the spinal cord that lead directly to the brain. Because morphine induces a response from the neuron, it is called an agonist. If it failed to cause a response, it would be considered an antagonist. Many of morphines derivatives are actually antagonists. Interestingly enough, if you replace the methyl group on morphine with a propenyl group, you end up with nalorphine, an antagonist with the ability to counter morphines effects. For morphine and its opioids, which are synthetic derivatives of the compound, there is a morphine rule that provides a recognizable format for these compounds, of which there are very few that deviate from the standard backbone structure. In the words of Bill Nye, Science Guy, Consider The Following:

The Morphine Rule

1. Morphine and its opioids have a tertiary nitrogen with a small alkyl substitute 2. Morphine and Co. have a quaternary carbon 3. There is a phenyl group or an isosteric equivalent directly attached to said q. carbon. 4. There is a two-carbon spacer between the quaternary carbon and the tertiary carbon. 5. Thats all, folks!

The process of extracting morphine was patented a while back by a Hungarian chemist, who used poppy straws to gather the drug. Jnos Kabay extracted the alkaloids from the crushed plant with

diluted sulfuric acid, a stronger acid than meconic acid (which was bound to the alkaloids in the opium), but not so strong as to react with the alkaloid molecules. A single batch of crushed poppy is extracted at least 6-10 times, so practically every alkaloid goes into the solution. The alkaloids are then precipitated from the solution obtained by either ammonium hydroxide or sodium carbonate. Purifying and separating out the morphine is the last step in this process. Its a lengthy business, and morphine isnt exactly good for us in the long run or the short one, for that matter. Morphine can dull pain, but it also alters ones mood and/or personality, can cause nausea and vomiting, stop your insides (bowels) from working properly its a great constipator and on top of its extreme inclination to being addictive, it causes fierce itching. Ouch. Normal morphine and its hydrated form are both only slightly soluble in water: in five litres of water, only one gram of the hydrate will dissolve. So pharmacies make sulfate and hydrochloride salts of morphine theyre 300 times more soluble than morphine itself. Theyre also acidic, as opposed to a saturated morphine hydrate solution, which has a basic pH of 8.5. Generally, morphine salts are mixed with a little NaOH to make them useful for medicinal purposes. Morphine is the active ingredient in opium. Early tests done with the compound showed that test subjects dosed with opium sans morphine had no effect on said subjects guinea pigs (go figure). Some interesting derivatives of morphine include methadone hydrochloride and codeine. The former was first marketed as Dolophine in honor of der Fhrer (it was made by AXIS during WWII as a painkiller and medicine), and is now used to treat heroin addiction. Codeine is an opioid used in Tylenol. Bet you didnt know you were taking mutated morphine for that headache, eh? One other thing. Heroin? That supremely addictive drug? That comes from morphine, too and it was named for its heroic ability to kill pain.

Jnos Kabay

Morphine in History
Morphine had its start, as did so many other things, in Mesopotamia, with the Sumerians, cerca 3400 B.C. These ancient people called it the joy plant, or Hul Gil, and from the Sumerians, the opium poppy travelled from the Assyrians to the Babylonians to the Egyptians, who would become famous for their poppy fields. Opium was a large source of trade in the early days, bringing all sorts of income to the early Eastern cultures. If we were to stop by 1100 B.C.,

around where the precursors to the Greeks lived on Cyprus, we would see that the desire to cultivate opium drove the production of surgical-quality knives before the fall of Troy to cut down opium poppy stalks. After Troy we had Hippocrates, hailed as the worlds first Father of Medicine. In 460 B.C. he disdained the mysticism that had grown up around opium whose active ingredient is morphine but noted its usefulness as a narcotic and medicine for womens diseases and such.
Hippocrates

Fast forward several hundred years, and we see the progression of opium through Persia, India, and China, through

such men as Alexander the Great and Arab traders. In 1200 A.D., opium from Egypt is being talked about in India, in such texts as the Dhanvantri Nighantu, where its uses as a medicine are described. But then, while opium is experiencing great popularity everywhere else, Europe turns her nose up at the product for about 200 years, starting in the 1300s. The cause? The Holy Inquisition, during which anything to do with the East was suddenly taboo. However, in 1500, the Portuguese get their paws on opium and start the trade right back up again, and for the next several centuries, laudanum or opium thebaicum, with some other nice stuff mixed in became very, very popular as a medicine. Opium became a cure-all of sorts, and by the 19th century, England was rolling in readily available vials of laudanum and raw opium. It was eaten, drunk, given to women for morning sickness, given to women for depression, given to children to keep them quiet (news flash! This still happens today. Many children are addicted to opium in countries such as India because nannies dose them until they are still.)but it was considered a medicine, not an addictive substance. Nonetheless, opium dens abounded in London and other wonderful places in England. China, on the other hand, was not at all happy with the opium trade, and on March 18, 1839, the Qing Dynasty went to war with England when the Chinese ordered all foreign traders to hand over their opium. Thus began the First Opium War, which the Chinese lost and they lost
Ah, Laudanum

Hong Kong to Britain, too. The Treaty of Nanjing, signed in 1842, was the result of the war launched by the biggest, richest, and perhaps most aggressive drug cartel the world has ever known: The British Empire. (A Brief History of Opium). Then followed the Second Opium War, after which a quarter of Chinese males found themselves addicted to opium. By this point, morphine had made its debut, and its most notable early use was during the American Civil War (as far as this country is concerned). Sadly, the American Civil War may well have been the source of todays problem of drug addiction in the old U.S. of A. Over 400,000 soldiers became addicted to morphine, and the drug was known widely as the army disease due to its potently addictive nature. In that day and age, with little medical expertise to help the injured and the dying, doctors did what they could which meant handing out painkillers and narcotics as though they were candy. About ten million opium pills were issued to Union soldiers, and opiates were used to treat anything from malaria to dystentry. It really got going with the advent of the syringe in 1853, and was sort of a poor-mans medicine. And much like in England, one could order opiates through the Sears catalogue in Americas late 1800s. But people started getting wise to opiums addictive nature, and morphine quickly went from being a cure-all to something that people regarded rather warily. The 1914 Harrison Narcotics Tax Act in the United States made it illegal to possess morphine. Cool fact, though: forensic scientists could search out morphine and its derivatives with a test: an unusual reaction with Mecke's reagent or, depending on who youre talking to, Lafons reagent. The reagent is made of selenious acid in concentrated sulfuric acid, and if morphine and the reagent react, you get a rather neat series of colors: green, then greenish blue would appear momentarily; transforming to blue, then slowly to a bluish green with a yellowbrown edge, and finally a rather olive green color would emerge. There are a few color tests that work this way and they give probable cause, really, instead of security in the fact that you have morphine, so more tests have to be done but its very interesting. Through a lot of regulation as a result of much effort over the past few decades, morphine has been registered as Schedule II drug. This means that it can be used carefully for medicinal purposes, but can also be readily abused. Morphine doses are carefully regulated, as well as determining who can sell it. As far as this compound goes, everything should be done with moderation and as far as the nations are concerned, with control. Its also illegal, apparently, to cultivate the opium poppy in the U.S.but amateur gardeners still grow the white, red, and yellow poppies in their flower beds next door. Take a look outside; you might be able to collect the fearsome seeds to use in your lemon-poppy muffins. Just mind that you dont eat them before going in for a drug test, since youll ring up as an opium user

if youre not careful. And if the muffin makes you feel drowsy and full, well, that might be the trace amounts of morphine working away on your nerves. I leave you with the following recipe, so that you can fiddle around with baking a doctors most potent painkiller into muffins. Enjoy!

Lemon Poppy Seed Muffins With Lemon Glaze

Makes 12 Muffins

For the Muffins: 2/3 cup sugar Grated zest 2 lemons Juice of 1 lemon 2 cups all-purpose flour 2 teaspoons baking powder 1/4 teaspoon baking soda 1/4 teaspoon salt 3/4 cup sour cream 2 large eggs 1 1/2 teaspoon pure vanilla extract 1 stick (8 tablespoons) unsalted butter, melted and cooled 2 tablespoons poppy seeds

For the Icing: 1 cup confectioners' sugar, sifted 2-3 tablespoons fresh lemon juice

Directions: Center a rack in the oven and preheat the oven to 400 degrees F. Line 12 molds in a regular-size muffin pan with paper muffin cups. Place the muffin pan on a baking sheet. In a large bowl, rub the sugar and lemon zest together with your fingertips until the sugar is moist and the fragrance of lemon strong. Whisk in the flour, baking powder, baking soda and salt. In a large glass measuring cup or another bowl, whisk the sour cream, eggs, vanilla, lemon juice and melted butter together until well blended. Pour the liquid ingredients over the dry ingredients and, with a rubber spatula,

gently but quickly stir to blend. Dont worry about being thorough a few lumps are better than over-mixing the batter. Stir in the poppy seeds. Divide the batter evenly among the muffin cups. Bake for 18 to 20 minutes, or until the tops are golden and a thin knife inserted into the center of the muffins comes out clean. Transfer the pan to a rack and cool for 5 minutes before carefully removing each muffin from its mold. Cool the muffins completely on the rack before icing them.

To make the icing: Put the confectioners' sugar in a small bowl and add about 1 1/2 tablespoons of the lemon juice. Stir with a spoon to moisten the sugar, then add enough lemon juice, a dribble at a time, to get an icing that is thin enough to drizzle from the tip of the spoon. Then drizzle lines of icing over the tops of the muffins or coat the tops entirely.

References

[Bill Nye, Science Guy] [Photo]. (2011). Retrieved from http://cdn.aceonlineschools.com/wp-content/uploads/2011/08/billnye1.jpg Booth, M. (1996). Opium: A History. In A Brief History of Opium. Retrieved from http://www.opioids.com/timeline/ Bradley, D. (1995). Structure of Morphine. Retrieved from Sciencebase and Elemental Discoveries website: http://www.sciencebase.com/structure_of_morphine.html A Brief History of Morphine. (1999). The Plant of Joy [Online text]. Retrieved from http://opiates.net/ Cartoon Laudanum [Cartoon sketch]. (n.d.). Retrieved from http://www.marriedtothesea.com/archives/2010/Jun/ Greek Myths and Greek Mythology. (n.d.). Morpheus, the God of Dreams. Retrieved from http://www.greekmyths-greekmythology.com/morpheus-the-god-of-dreams/ Greenspan, D. (n.d.). Lemon Poppy Seed Muffins with Lemon Glaze [Yum.]. Retrieved from Pickycook.com website: http://www.pickycook.com/breakfastandbrunch/lemonpoppyseedmuffinswithlemonglaze.aspx [Hippocrates] [Sculpture]. (n.d.). Retrieved from http://stansgreatbooksblog.blogspot.com/2011/05 bible-and-hippocrates-on-hemorrhoids.html [Jnos Kabay photograph] [Picture]. (n.d.). Retrieved from http://hgabriella.blogspot.com/2010/12/114-eve-szuletett-kabay-janos.html

Morphine. (n.d.). Retrieved from Department of Chemistry, Rochester University website: http://www.emsb.qc.ca/laurenhill/science/morphine.html Morphine and Heroin. (n.d.). Retrieved from http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/morphine_text.htm Morphine Chemistry. (n.d.). Retrieved from News Medical website: http://www.news-medical.net/health/Morphine-Chemistry.aspx Morphine: It's History and Uses. (2004). Retrieved from AnapolSwartz: Attorneys at Law website: http://www.anapolschwartz.com/practices/ethex-morphine-recall/morphinehistory-uses.asp Nature's Pharmacy: Ancient Knowledge, Modern Medicine. (n.d.). Papaver somniferum opium poppy. Retrieved from University of Iowa Medical Museum website: http://www.uihealthcare.com/depts/medmuseum/galleryexhibits/naturespharmacy/papaverplant/p oppy.html Opium Poppy [Sketch]. (n.d.). Retrieved from http://www.botanical.com/botanical/mgmh/p/popwhi64-l.jpg [Structure of Morphine] [Computer-made chemical structure]. (n.d.). Retrieved from http://www.sciencebase.com/structure_of_morphine.html