Narcotic analgesics.

There is documentation of the use of opium derived products in the ancient history of the Assyrians: the Egyptians; in the sixth century AD by the Roman Dioscorides; and by Avicenna (980-1037). Reference to opium like products is made by Paracelsus and by Shakespeare. Charles Louis Derosne and Fredrich Wilhelm Adam Serturner isolated morphine from raw opium in 1802 and 1806 respectively, and it was Sertürner who named the substance morphine, after Morpheus, the Greek God of dreams. By the middle 1800s, Opium and related opioid derived products were the source of a major addiction in USA, and to some extent in the United Kingdom. Opioid products are of major therapeutic value in the treatment of pain from injury, post surgery, intractable pain conditions, and some forms of terminal cancer.

DARK Classics in Chemical Neuroscience: Morphine.

As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex phenanthrene alkaloid produced by Papaver somniferum, morphine has fascinated chemists seeking to disentangle pharmacologically beneficial analgesic effects from addiction, tolerance, and dependence liabilities. In this review, we will detail the history of morphine, from the first extraction and isolation by Sertürner in 1804 to the illicit use of morphine and proliferation of opioid use and abuse disorders currently ravaging the United States. Morphine is a molecule of great cultural relevance, as the agent that single-handedly transformed our understanding of pharmacognosy, receptor dynamics, and substance abuse and dependence disorders.

The Chemical History of Morphine: An 8000-year Journey, from Resin to de-novo Synthesis.

Evidence of human use of opium dates back as far as the sixth millennium BCE. Ancient societies through the Renaissance period created a variety of opium products, proliferating its common use and subsequent addiction. Because the active moiety was not known at this time, the potency of these opium concoctions could neither be predicted nor controlled. The first step in identifying opium's active ingredient, morphine, was its chemical isolation in the early 1800s by Wilhelm Sertürner. The subsequent elucidation of morphine's chemical formula and Sir Robert Robinson's derivation of morphine's structural formula, which won him the 1947 Nobel Prize in Chemistry, round out 150 years of the incremental advances in our chemical understanding of morphine. Nevertheless, our attempts to synthesize morphine, despite our advanced knowledge in synthetic chemistry, are still no match for the plant-based extraction of morphine from the poppy plant. The status quo remains problematic socially, economically, and politically; the relationships between the countries laboriously growing poppy plants to extract morphine and those countries importing these painkillers are unstable at best. In this study, we contrast the cumulative scientific discoveries that have led to our current chemical knowledge of morphine with the centuries-old natural method of morphine production that still dominates the opioid market today.

Maestro, Marguerite, morphine: The last years in the life of Mikhail Bulgakov.

The manuscript pages of the final draft of Master i Margarita, the masterpiece by Mikhail Bulgakov, written in the last four years of his life (1936-1940), have been treated with a mixture of chromatographic beads, namely a strong cation exchanger and a C8 resin. Potential substances captured by the beads, after harvesting them, were eluted with a mixture of isopropyl alcohol, dichloromethane and ammonium hydroxide and the eluate subjected to GC-MS analysis in order to detect the presence, if any, of drugs, due to the fact that the writer suffered intense pains caused by an inherited nephrotic syndrome. Indeed all the pages under investigation (a total of ten, taken at random among 127 foils) contained traces of morphine, from as little as 5 up to 100ng/cm(2). In addition to the intact drug, we could detect one of its metabolites, namely 6-O-acetyl morphine. The significance of these findings in terms of a possible improvement of the novel and in terms of drug use (or abuse) in the modern world is discussed and evaluated. BIOLOGICAL SIGNIFICANCE: The extraction of metabolites/proteins from the surface of the original manuscript pages of Bulgakov masterpiece Master i Margarita has permitted to monitor his health state and intake of medicaments over the last four years of his life. We have ascertained that: (1) he was assuming large doses of morphine as pain killers; (2) he was affected by a nephrotic syndrome, since we could identify three proteins known as biomarkers of this pathology. The double extraction procedure here reported could open up a novel field of investigation of (relatively) ancient manuscripts for metabolome/proteome analysis on the health status of the writer/artist.

On the history of opium / Z dziejów opium.

Most likely, opium was the first narcotic substance discovered at the dawn of humankind. The history of drug addiction is immensely rich and allows for tracing the long way humankind had to travel to reach the contemporary level of consciousness with respect to narcotic substances. A retrospective view of drug addiction that takes into consideration the historical context, while extending our knowledge, also allows for a better understanding of today's problems. The report presents elements of a retrospective view of problems associated with addiction to opium, morphine and heroin over the centuries, what is a subject of scientific interest in contemporary toxicology.

[Obligatory documentation for narcotic drugs over the course of time : the morphine and cocaine book for physicians according to the 1930 parliamentary law gazette]. / Dokumentationspflicht für Betäubungsmittel im Wandel der Zeit : Das Morphin- und Kokainbuch für Arzte nach dem Reichsgesetzblatt 1930.

According to the opium law and prescription statute of 1930, physicians were duty-bound to maintain a stock ledger to allow a traceable record of the location of narcotic drugs. If a simplification of the prescription of opiates was welcomed 10 years ago then 2 years after amendment of the addictive drugs statute thought should be give to safe use, as can be concluded from a morphine logbook from the time of the introduction of the Federal opium law. "Receipt and issue... deliverer and recipient" must be able to be extracted from the documentation, which means the delivery and the dispensing but not the individual application.

William Osler, urolithiasis, and God's own medicine.

OBJECTIVES: To identify the contributions of Sir William Osler, who is regarded as the pre-eminent physician of his time, to urology, both objective and subjective. METHODS: A search of Osler's bibliography of over sixteen hundred publications, as well as his observations, some hitherto unpublished, on the episodes of renal colic that he personally experienced, was conducted. Osler was treated with morphine, which he characterized as "God's own medicine," and the origin of this description is explored. RESULTS: Osler published over 50 articles devoted to urologic topics, including 2 on vaginismus and Peyronie's disease; the former, by his fun loving alter ego, Egerton Yorrick Davis, was a hoax. Osler discusses urolithiasis and renal colic in his magnum opus, The Principles and Practice of Medicine, citing Montaigne's self description of his suffering as "unexcelled." Osler later personally experienced 2 episodes of renal colic, which he graphically and eloquently describes in his Lumleian Lectures of 1910. His descriptions of renal colic before and after his own experience are compared in the light of Plato's comment that a physician should experience the disease that he treats. CONCLUSIONS: William Osler was one of those giants who, in the early days of specialization, took all of medicine for their own. His contributions to urology were significant and include his descriptions of his own episodes of renal colic and the use of morphine-"God's own medicine."

[History of pain treatment from 1500 to 1900]. / Geschichte der Schmerztherapie 1500 bis 1900.

The history of pain treatment likely started in the cradle of mankind, as the experience of pain from many causes presumably had an aversive dimension comparable in its ranking to elementary sensations and motivations such as hunger, thirst, maintenance of body temperature, and sexuality-all vital for individual and genetic survival. Thus, pain certainly was among the drives to create social behavior and medicine-these functions still are inherent in pain. The period of history from 1500, as considered here, is dominated by the emergence of science. The exploration of the inside of the human body found the brain to be the seat of sensations, emotions, and behavior, and this progress included pain as well, slowly disabusing it from the magic elements and demons still inherent from early times. The rational phase of medicine began and also included new concepts of pain as first conceived by Descartes. The treatment and prevention of pain became a strong motive of medicine, with new approaches in drug treatment, physical applications such as electricity, and discoveries of psychosocial implementations. During the nineteenth century the most important breakthroughs in pain treatment included general and local anesthesia as well as analgesic drugs from morphine to anti-inflammatory agents. They succeeded in taking the terror out of the agonizing pain of surgery and dramatic courses of diseases. Today's natural extension of the medical success in controlling acute pain may be seen in the period of pain medicine aimed at understanding and preventing chronic pain.

El dolor y su tratamiento a través de la historia / Pain and its treatment over history

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