Morphine and Opium Alkaloids
Presented by Adam Wrobel
 
 

Opium is a drug that serves as the source of several
medicines, including codeine, papaverine,
thebaine, and morphine.

 

 

Poppy Plant is 
a Source 
of Opium 


 

History Structure of Morphine Related Alkaloids Source & Isolation Areas Grown
Physiological Effects & Mechanism of Action Morphine Biosynthesis Conclusion Links & References
 
Scientific Name
Papaver Somniferum L.

Family
Poppy family – Papaverace

Habitat
Balkans, Middle East, India and China

Alkaloids
morphine, codeine, 
papaverine thebaine, 
and narceine

Main Alkaloid
morphine 
(C17 H19 NO3)

Active Parts
The opium or latex 
produced by doing 
a cut in the walls 
of the capsule.

Medicinal Properties

Analgesic and somniferous

 

History of Opium




The use of opium began at least 6,000 years ago in the Middle East. Greek and Roman physicians prescribed the drug before the time of Christ. Arabian traders took opium to China and India, probably starting in the A.D. 600's.

At first, the Chinese used the drug chiefly as a medicine. European traders introduced opium smoking into China in the early 1600's. The Chinese government outlawed opium in 1729, but traders continued to exchange it for silk, porcelain, and other Chinese products. In the late 1700's, opium addiction became widespread among the Chinese

During the 1800's, people in the United States and Europe could buy laudanum, morphine, and other opiates legally and without a prescription. By 1900, at least 200,000 Americans had become addicted to opiates.

The Harrison Act, a group of laws passed in 1914, greatly reduced the problem in the United States. Addiction to opiates particularly heroin began to increase in the late 1940's and has continued to rise ever since. Today, a number of nations and international organizations cooperate in fighting the illegal manufacture and sale of opium and opiates.
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Structure of Morphine
 

http://www.druglibrary.org/schaffer/heroin/morphinemolecule.htm


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Related Alkaloids



 

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Source and Isolation


The flower's botanical name is papaver somniferum. The Sumerians called it Hul Gil, 'flower of joy.'

The flower is grown mainly by impoverished farmers on small plots in remote regions of the world. It flourishes in dry, warm climates and the vast majority of opium poppies are grown in a narrow, 4,500-mile stretch of mountains extending across southern Asia from Turkey through Pakistan and
Laos.

About three months after the poppy seeds are planted, brightly-colored flowers bloom at the tips of greenish, tubular stems. As the petals fall away, they expose an egg-shaped seed pod. Inside the pod is an opaque, milky sap. This is opium in its crudest form.

The sap is extracted by slitting the pod vertically in parallel strokes with a special curved knife. As the sap oozes out, it turns darker and thicker, forming a brownish-black gum. A farmer collects the gum with a scraping knife, bundles it into bricks, cakes or balls and wraps them in a simple material such as plastic or leaves.

At the laboratory the opium is mixed with lime in boiling water. A precipitate of organic waste sinks to the bottom. On the surface a white band of morphine forms. This is drawn off, reheated with
ammonia, filtered and boiled again until it is reduced to a brown paste. Poured into molds and dried in the sun, it is now morphine base, which has the consistency of dense modeling clay.
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Areas Where Opium is Grown
 

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Physiological Activity and Mechanism of Action



Opium ranked as the most effective pain-relieving drug until the development of morphine in the early 1800's. Opium was also used to stop coughing and diarrhea, to ease worry, and to cause drowsiness. Opiates serve many of the same purposes today.

Opium contains about 24 alkaloids, but only 2, morphine and codeine, have much clinical use. A small fraction of opium contains thebaine, which has anticonvulsant activity similar to strychnine. The principal alkaloid of opium (about 10%) is morphine. Physicians prescribe morphine to relieve severe pain. Codeine, probably the most widely used opiate, stops coughing. The opiate paregoric controls diarrhea.

Morphine and other opiates bind to several kinds of opiate receptors also used by endorphins (pain mediators produced by our own bodies).

Endorphins and opiates are structurally similar.
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Morphine Biosynthesis



The biological pathway from the primary metabolite L-tyrosine to (S)-reticuline, the universal precursor to a large variety of isoquinoline alkaloids in plants, is established in precise detail at the enzyme level. The conversion of (S)-reticuline to its (R)-epimer opens the morphine pathway, which is restricted in the plant kingdom to certain members of the genus Papaver . While the precursor molecule (R)-reticuline only contains three rings with one asymmetric center, the morphine skeleton consists of five rings with five asymmetric centers. Crucial C-12-C-13 bond of morphine alkaloids that generates the fourth ring can be envisaged as being formed by ntramolecular phenolic coupling of (R)-reticuline.

Indeed, experimental proof at the precursor feeding level to whole plants has been obtained that (R)-reticuline is transformed to salutaridine by regioselective para-ortho oxidative coupling. The biocatalyst from opium poppy catalyzing this important step has been discovered recently and found to be a cytochrome P-450 enzyme system.(R)-Reticuline is thus converted in the presence of O and NADPH to salutaridine that is in turn reduced stereoselectively to salutaridinol with (7S)-configuration. Only this (7S)-alcohol and not its (7R)-epimer is transformed into thebaine in vivo. This transition involves the closure of the oxide bridge between C-4 and C-5 of salutaridinol, thus generating thebaine, the first biogenetic precursor of morphine containing the pentacyclic ring system. Salutaridinol possesses the correct (7S)-configuration for an allylic syn-displacement of the activated hydroxyl by the phenolic hydroxyl that follows the precedented stereocontrol for S2` substitution of cyclohexene rings.

While both alcohols, (7S)-salutaridinol and its biologically inactive (7R)-epimer, can under acid catalysis easily form thebaine, theplant enzyme system strictly discriminates against the unnatural epimer. The mechanism for this discrimination and the mechanism of oxide bridge formation have been a matter of considerable speculation.
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Conclusion

Till this day scientists were unable to synthesize a more effective analgesic than morphine or some of its semi-synthetic or synthetic analogs. Etorphine for example is a semi-synthetic cousin of morphine. The potency of etorphine is extremely impressive. One mg is capable of immobilizing a rhinoceros weighing 2000 kg. A dose of 4 mg is capable of immobilizing an African elephant weighing 5000 kg!
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Links and References


The Opiates

http://www.druglibrary.org/schaffer/heroin/opiates.htm

Opium Throughout History

http://www.pbs.org/wgbh/pages/frontline/shows/heroin/etc/history.html

Effects of Opium, Morphine, and Heroin on Addicts

http://www.druglibrary.org/schaffer/Library/studies/cu/cu4.html

Opioid Pain Killers Available in the US

http://www.druglibrary.org/schaffer/heroin/opifaq2.htm

Opiates for Pain Relief, for Tranquilization, and for Pleasure?

http://www.druglibrary.org/schaffer/Library/studies/cu/cu2.html

The Opiate Receptor

http://www.sfn.org/briefings/opiate.html

The Brain's Response to Opiates

http://www.nida.nih.gov/MOM/OP/MOMOP1.html

Booth, Nicholas H., McDonald Leslie E., Veterinary Pharmacology

and Therapeutics. Iowa State University Press. Ames, Iowa 1992.


Rainer Lenz , Meinhart H. Zenk Acetyl Coenzyme

A:Salutaridinol-7-O-Acetyltransferase from Papaver somniferum Plant Cell Cultures The Enzyme Catalyzing the Formation of Thebaine in Morphine Biosynthesis Journal of Biological Chemistry, Volume 270, Number 52, December 29, 1995 pp. 31091-31096


Dr. Friesen's web page


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