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.

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.

[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.

[History of opium poppy and morphine]. / Opiumsvalmuen og morfin gennem tiderne.

Opium has been known for millennia to relieve pain and its use for surgical analgesia has been recorded for several centuries. The Sumerian clay tablet (about 2100 BC) is considered to be the world's oldest recorded list of medical prescriptions. It is believed by some scholars that the opium poppy is referred to on the tablet. Some objects from the ancient Greek Minoan culture may also suggest the knowledge of the poppy. A goddess from about 1500 BC shows her hair adorned probably with poppy-capsules and her closed eyes disclose sedation. Also juglets probably imitating the poppy-capsules were found in that period in both Cyprus and Egypt. The first authentic reference to the milky juice of the poppy we find by Theophrastus at the beginning of the third century BC. In the first century the opium poppy and opium was known by Dioscorides, Pliny and Celsus and later on by Galen. Celsus suggests the use of opium before surgery and Dioscorides recommended patients should take mandrake (contains scopolamine and atropine) mixed with wine, before limb amputation. The Arabic physicians used opium very extensively and about 1000 AD it was recommended by Avicenna especially in diarrhoea and diseases of the eye. Polypharmacy, including a mixture of nonsensical medications were often used. Fortunately for both patients and physicians many of the preparations contained opium. The goal was a panacea for all diseases. A famous and expensive panacea was theriaca containing up to sixty drugs including opium. Simplified preparations of opium such as tinctura opii were used up to about 2000 in Denmark. In the early 1800s sciences developed and Sertürner isolated morphine from opium and was the founder of alkaloid research. A more safe and standardized effect was obtained by the pure opium. Several morphine-like drugs have been synthesized to minimize adverse effects and abuse potential. Opioid receptors were identified and characterized in binding assays and their localization examined. However, the complexity of the system including interaction with several neurons and transmitters indicate the goal of nonaddictive opiates to be elusive. Combination therapy, innovative delivery systems and long-acting formulations may improve clinical utility.

In the arms of Morpheus the development of morphine for postoperative pain relief.

PURPOSE: To analyse the historical development of morphine for postoperative analgesia and how this development was shaped by the evolution of anesthetic techniques. METHODS: After a systematic review of the literature, information was gathered from primary sources. PRINCIPAL FINDINGS: In ancient medicine, some plant derivatives were used to alleviate pain including: alcohol, cannabis, mandrake, and opium. Over the past two centuries, opium and its derivatives have become the most widely used analgesics for severe pain. Before the development of general anesthesia, surgery was only performed out of extreme necessity. It is probable that an analgesic such as opium would have been given following surgery although its use may not have been recorded. The first description of postoperative opium was by James Moore in 1784. Morphine was isolated from opium by Friedrich Serturner in 1805. However, it was not until the development of the hypodermic needle and syringe nearly 50 yr later that the use of morphine became widespread. Over the last century, various delivery systems for morphine have been developed including subarachanoid and epidural injection, and more recently patient-controlled intravenous, epidural and intranasal analgesia. In addition, many new opioids have been synthesized. CONCLUSION: Since its isolation from opium almost 200 yr ago, morphine remains the most widely used analgesic and the standard against which all new opioids for postoperative pain relief are compared.

Receptores opioides a la luz de la biología molecular: explican mas de 6.000 años de farmacología empírica / Opioid receptors in the era of molecular biology: explain more than 6.000 years of empiric pharmacology

The medicinal use of opium and of morphine in different cultures and ancient civilizations is described. Research within the past 40 years have demonstrated the existence of brain opiate receptors. Morphine and related opioid analgetic interact at these sites in the nervous system to produce the characteristic pharmacological effects of these drugs. The opiate receptors have structural homologies with a variety of other cell membrane recpetors; they activate second messenger-based chemical transduction systems in the cell embrane and are endowed with several regulation mechanisms. These opiate receptors are presumably activated under specific physiological conditions by endogenous ligands (opiopeptins). It is currently thought thar morphine mimicks the opiopeptins by interacting with these receptors either at different molecular subsites or with a different mode of action