Codeine from Papaver somniferum

Opium, the sun-dried latex of the unripe fruit of Papaver somniferum, cultivated from early times for this drug, contains at least 23 alkaloids. Of the major alkaloids three—morphine, codeine, and thebaine—contain the morphinan ring system. 

The term opioid refers to any exogenous substance that acts as an agonist at any of several receptors. Opioid antagonists are drugs that bind to a receptor but produce no actions. The poppy plant, Papaver somniferum, from which opium is obtained, is grown in many areas of the world. Morphine constitutes 10% of opium, and codeine can be obtained direcdy from opium. Semisynthetic opioids such as heroin and oxycodone are obtained directly or indirectly from morphine. There are other distinct chemical classes of drugs with opioid actions, including the methadones. 

Opium The extract from Papaver somniferum containing morphine and codeine. 

Morphine (10) and codeine (11), constituents of opium, are the most interesting alkaloids found in nature. Morphine is also the oldest alkaloid isolated, in 1805, by the German pharmacist Sertiimer from opium, the sun dried latex of Papaver somniferum. The structure of morphine with its so-called morphinan skeleton, once called the acrobat under the alkaloids, was finally elucidated in 1952 by the first total synthesis performed by Gates and Tschudi. Many syntheses would follow [26], but all morphine used today, whether legal or illicit, originates in the natural source P. somniferum or its extract, opium. The latex may contain up to 20% morphine. Most legal morphine is converted into the anticough medicine codeine (Table 5.1) by treatment with trimethylanilinium methoxide, whereas almost all illicit morphine is acetylated to the diacetate heroin. 

Opium is a cmde exudate obtained from the opium poppy Papaver somniferum, and it provides several medicinally useful alkaloids. One of these is codeine, which is widely used as a moderate analgesic. Opium contains only relatively small amounts of codeine (1-2%), however, and most of the codeine for dmg use is obtained by semi-synthesis from morphine, which is the major component (12-20%) in opium. Conversion of morphine into... 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

Morphine and cocaine Morphine is medically the most important alkaloid present in opium. Opium itself consists of the dried milky exudate extracted from unripe capsules of the opium poppy (Papaver somniferum), which is grown mainly in Asia, but also in some parts of India and China. Morphine is a powerful analgesic and has been used to treat severe pain. However, its addictive properties complicate its long-term medical use and it is also a drug of abuse. In addition to morphine, opium also contains codeine, which has similar, but weaker, actions. 

Like morphine, codeine is extracted from natural opium, obtained from the poppy plant (Papaver somniferum). Only when it was first discovered and tested was codeine purified directly from opium (see Chapter 1). Today pharmaceutical-grade codeine is synthesized from morphine through the relatively simple chemical modification process of methylation, whereby CHj replaces a hydrogen atom on the morphine molecule. The chemical substitution reaction that takes place (H for CHj) does so at a specific location on the morphine molecule (Figure 3.1) if the substitution were to occur elsewhere on... 

The opium is obtained from the opium poppy Papaver somniferum. It contains two type of alkaloids e.g. phenanthrene derivatives (morphine, codeine thebaine) and benzyl isoquinoline derivatives (papaverine and noscapine). 

Thebaine, codeine and morphine from poppy straw (Papaver somniferum) were extracted with carbon dioxide and various polar modifiers at 20 MPa and 40.5 °C. Kinetic extraction curves for morphine showed that 50% methanol in carbon dioxide was necessary in order to achieve quantitative yields in less than 20 min. A mixture of 25% methanol, 0.22% methylamine and 0.34% water had the same effect as 50% methanol in the catbon dioxide. However, it was also reported that, in spite of its strong extraction power, the methylamine-water mixture had a major drawback in that morphine in the presence of the amine degraded in the presence of light. Hence, carbon dioxide-methanol-water mixtures were investigated increasing the water content in the extraction fluid dramatically enhanced the extraction rate for thebaine [29]. 

The opium alkaloids, which are obtained from Papaver somniferum, contain two groups of compounds compounds with phenanthrene derivatives, consisting of morphine, codeine, and thebaine and compounds with isoquinoline derivatives, consisting of papaverine and noscapine. 

Codeine is extracted from opium. Opium is a chemically complex drug derived from a flowering plant, the opium poppy. The scientific name for the opium poppy is Papaver somniferum, which translated from Greek means poppy that causes sleep. Opium is produced by drying the thick liquid harvested from the unripe seed capsule of the flower. It contains several different medically important chemicals known as alkaloids (non-acidic chemicals), the most important being morphine and codeine. 

The isolation of morphine from opium and the recognition of the significance of its physiological effects by F. W. A. Sertiirner in 1803-1817 as well as the first definition of the term alkaloid by Meissner in 1819-1821 have led to a rapid progress in the research of alkaloids (1). In the beginning of the past century, much attention was paid to the cultivated poppy plant Papaver somniferum L., which has been used since time immemorial in popular medicine. Of the so-far known 41 opium alkaloids, only morphine, codeine, and papaverine have found... 

Opium is obtained from the dried juice from the seed capsule of the oriental poppy, Papaver somniferum. The dried juice contains up to 17% morphine and 4% codeine by weight, as well as other, non-additive alkaloids that lack analgesic activity such as noscapine, papaverine, and thebaine. Papaveretum is a standardized preparation of opium containing 50% morphine. 

Varieties of Papaver somniferum with varying content of morphine alkaloids have been studied, and varieties having a genetically governed low alkaloid content have been identified.143 The dynamics of the variation of amount of morphine and codeine present in P. somniferum with time of harvesting of the capsule have been studied.144 The thebaine content of P. bracteatum in relationship to plant development has been studied, and strains have been isolated from which may be obtained a dried latex that contains >55% thebaine, corresponding theoretically to a yield of 58 kg ha-1 or approximately 50 kg ha-1 from harvested capsule.145... 

Isolation of the alkaloids from the latex of the opium poppy, Papaver somniferum, led to the identification of over 20 compounds (Fig. 11.1). The most abundant alkaloids were morphine (1), codeine (2), thebaine (3), noscapine (4), and papaverine (5). 

Opium is an alkaloid obtained from the dried latex of incised unripe flower pods of the poppy plant Papaver somniferum and is comprised of as many as 25 different alkaloids, including pharmacologically active morphine, codeine, and papaverine. Opium is cultivated in Southeast Asia, Turkey, Pakistan, Afghanistan, India, Iran, Nigeria, and Mexico. Heroin is produced by acetylation of morphine. 

The medical uses of morphine alkaloids have been known at least since the seventeenth century, when mide extracts of the opium poppy. Papaver somniferum, were used for the relief of pain. Morphine was the first pure alkaloid to be isolated from the poppy, but its clgsc relative, codeine, atso occurs naturally. Codeine, which is simply the rtethyl ether of morphine and is convert to morphine in the body, is ufed in preacription cough medicines and as an analgesic. Heroin, another close relative of morphine, does not occur naturally but is synlhesiiced by dlacotylalioii nf morphine. 

The capsules and stems of Papaver somniferum contain opiate alkaloids essential in medicine. They are classified into two groups, phenanthrene types (morphine, codeine, thebaine) and benzylisoquinoline types [papaverine and noscapine(narcotine)]. These two types of alkaloids show sharply specific pharmacological properties. It is noteworthy that morphinane alkaloids are formed from (-)-(/ )-reticuline, whereas most other alkaloids derive from (-l-)-(5)-re-ticuline 11). 

Use of the opium poppy (Papaver somniferum) to ameliorate pain dates back thousands of years, and the active metabolite morphine (2) was isolated first from its extracts in 1806 followed by codeine (53) in 1832 (27, 28). Morphine and its derivatives are agonists of opiate receptors in the central nervous system and are some of the most effective pain relievers known and prescribed for postoperative pain. Morphine and codeine differ by substitution by methyl ether. Unfortunately, addictive properties of these compounds limit their use. Efforts have been made to reduce the addictive properties of morphine, which resulted in a semisynthetic derivative buprenorphine (54) (29). This compound is 25 to 50 times more potent than morphine with lower addictive potential and has been indicated for use by morphine addicts. 

Opiates are compounds extracted from the milky latex contained in the unripe seed pods of the opium poppy (Papaver somniferum). Opium, morphine, and codeine are the most important opiate alkaloids found in the opium poppy. Opium was used as folk medicine for hundreds, perhaps thousands of years. In the seventeenth century opium smoking led to major addiction problems. In the first decade of the nineteenth century, morphine was isolated from opium. About 20 years later, codeine, one-fifth as strong as morphine, was isolated from both opium and morphine. In 1898, heroin, an extremely potent and addictive derivative of morphine was isolated. The invention of the hypodermic needle during the mid-nineteenth century allowed opiates to be delivered directly into the blood stream, which increases the effects of these drugs. Synthetically produced drugs with morphine-like properties are called opioids. The terms narcotic, opiate, and opioid are frequently used interchangeably. Some common synthetically produced opioids include meperidine (its trade name is Demerol) and methadone, a drug often used to treat heroin addiction. 

Semi-Synthetic Transformations of the Morphine Alkaloids Although it has been synthesised (ref 61), (now by four distinct routes) morphine (63), a powerful analgesic is readily available from the natural source, opium obtained from Papaver somniferum as the major alkaloid present (approx. 10%) and indeed the first to be isolated by Serturner in 1803, while the methyl ether, codeine (64) which comprises only 0.5% is relatively weakly active. Thebaine (65) a third component of opium is non-analgesic but is important as an intermediate for the formation of codeine, a somewhat scarce commodity (ref. 62) but a valuable mild analgesic and anti-tussive in great demand. It is best prepared from morphine by methylation with phenyl trimethylammonium ethoxide the by-product consisting of dimethylaniline (ref.63). 

Opium poppy Papaver somniferum L., Papaveraceae) is one of the most important medicinal plants and has been cultivated since early centuries. Opium, the dried cytoplasm of a specialized internal secretory system called the laticifer, is normally collected from the unripe capsule. It is the source for the commercial production of medicinally important alkaloids, morphine, codeine, thebaine, noscapine and papaverine [130, 131], Fig. (61). Morphine, which has strong addictive property, is still the most effective analgesic for the treatment of mortal cancer patients in modem medicine. Codeine is commonly used as an antitussive. However, field cultivation of this plant has been limited since 1953 by the United Nations Opium Conference Protocol to prevent narcotic crimes. Therefore, establishing tissue culture technique for the production of morphinan alkaloids seems to be desirable not only for medicinal purpose but also for decreasing abuse of opiates. 

Novoseven eptacogalfa factor VII. noscapine [ban, inn] (narcotine i-a-narcotine) is an alkaloid from Corydalis cava (Corydalis tuberosa), Papaver somniferum and other Papaver spp. It is a by-product in extraction of morphine from opium, and one of the first alkaloids to be isolated. It can be used as a centrally acting ANTITUSSIVE, similar in pharmacology to codeine, novobiocin [ban, inn] (Albamycin ) is an antibiotic with ANTIBACTERIAL activity against Gram-positive bacteria. It is also a LEUKOTRIENE RECEPTOR ANTAGONIST. 

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