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Synthetic Opiates

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Introduction

Humans have constantly searched for effective and safe relief from pain. One pain reliever, used from antiquity, has been opium derived from poppy plants. In the nineteenth century, the pain killers morphine, codeine, and thebaine were isolated from opium. Morphine and codeine quickly became important medicines for treating pain, cough, and diarrhea. This exhibit tells how 20th century researchers at the National Institutes of Health created new opiate drugs and developed a synthetic source for morphine and codeine -- and why.

The Drug Design and Synthesis Section of the Laboratory of Medicinal Chemistry (LMC) is part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Its mission is to identify the structure and function of chemical messenger systems in the brain and to determine how drugs, especially opium, affect the brain on a molecular level.

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The Drug Design and Synthesis Section of the Laboratory of Medicinal Chemistry (LMC) group

Photograph of The Drug Design and Synthesis Section of the Laboratory of Medicinal Chemistry (LMC) group
Seated in the first row Ross Johnson, Marina Mattson, Kenner Rice, Margaret Aein, Arthur Jacobson. Standing in the middle Row are: Dorota Mateka, Neil Grayson, Guerdy Toussaint, Lilian Radesca, Celia Dominguez, Zi-Qiang Gu, Brian de Costa. Standing in the third and final row are: Dragona Tadic, Wanda Williams, Xiao-Shu He, Dorothea Thomasson, Jan Linders, Wayne Bowen, John Glowa, Bertold Vilner. (December 1991).

From Flower to Medicine

Sap from the poppy Papover somniferum has been used for thousands of years to relieve pain and treat symptoms of disease.

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Sap from the poppy Papover somniferum (pictured below) has been used for thousands of years to relieve pain and treat symptoms of diseases.Image Added
The poppy Papover Somniferum

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Raw Opium Oozes from a Lanced Poppy Seed PodImage Added

Raw opium oozes from a lanced poppy seed pod grown by licensed farmers in Turkey and Iran. Poppies are grown only in certain areas of the world, and supply the entire world’s supply of opiate pain killers.

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A brick of raw pressed opiumImage Added
A brick of pressed raw opium ready to be transported for processing.

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Creating New Drugs by Modifying the Molecule

When scientists first began looking at drugs derived from opium ("opiates"), they were interested in identifying drugs that would be good painkillers, but would not lead to patients' becoming addicted to the drug -- a problem with codeine and morphine.

In 1929, Dr. Lyndon F. Small established the Drug Addiction Laboratory, the ancestor of today's LMC. Seeking to create painkillers which would not cause addiction, Small studied and modified the morphine molecule and related opium products. This work was based on the assumption that the drug's effects were directly related to its molecular structure. Small's assumption proved correct. Metopon, a potent opiate painkiller, was among his most notable contributions. With metopon, partial separation of the painkilling effects from the undesired addictive property was at last achieved. This finding was the underpinning of much research that continues today into a total separation of painkilling and addictive effects.

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Dr. Small prepared hundreds of potential opiate drugs for pharmacological evaluation, keeping them in cigar boxes. Small's samples have been used by many investigators to identify opiate products.

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