Opium analgesics

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... 

Opiates Compounds derived from, or similar in action to, potent analgesic opium alkaloids. 

Opiates are medications derived from the poppy plant that attach to opioid receptors in the brain. The extraction of morphine from opium marked the beginning of organic alkaloid chemistry and has led to the synthesis of a variety of semisynthetic and synthetic analgesics. Opium and its derivatives have been used for thousands of years not only for pain relief but also for the euphoria that they produce. It is this dual effect that allows them to be so useful but also addictive and therefore dangerous. Understanding their stmcture, action, use, and abuse reflects the close connection that we have with the plant world. 

An opium alkaloid Although it is an excellent analgesic its use is restricted because of the potential for addiction Heroin is the diacetate ester of morphine )... 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Enkephalins and Endorphins. Morphine (142), an alkaloid found in opium, was first isolated in the early nineteenth century and widely used in patent medicines of that eta. It is pharmacologically potent and includes analgesic and mood altering effects. Endogenous opiates, the enkephalins, endorphins, and dynotphins were identified in the mid-1970s (3,51) (see Opioids, endogenous). Enkephalins and endorphins ate Hsted in Table 9. 

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Opioids. Morphine [57-27-2] C yH NO, (8) the most prevalent and analgesicaHy potent of the naturally occurring opium alkaloids (qv), has been used as an anesthetic premedication for over one hundred years (93). It has also been used as an iv analgesic for the last four decades, and, since 1969, in high doses as an anesthetic agent (117). 

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

Papaverine (107) is among the host of minor alkaloids that have been isolated from opium. The compound is distinct in its biologic activity from many of the other opium constituents in that it does not exhibit any analgesic activity. Instead, papaverine acts as a nonspecific spasmolytic agent. As such, it has found... 

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

Opioid analgesics are the narcotic analgesics obtained from the opium plant. More than 20 different alkaloids are obtained from the unripe seed of the opium poppy... 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

The development of the first effective analgesic drug, opium, was almost certainly adventitious, and occurred in prehistoric times. The use of the dried exudate from slitting the immature capsule of the opium poppy, Papaver somniferum, as an analgesic, sedative and euphoriant, has a long folkloric history. Isolation of the principal active component morphine (1) as a pure crystalline compound represented one of the early landmarks in organic chemistry. 

Opium and its derivatives have been employed for centuries for the treatment of pain. Morphine was first synthesized in 1805 and has proven to be one of the most effective analgesic agents available [1], Morphine and its analogs are particularly useful because they diminish pain sensation while maintaining consciousness. However, opiates induce severe side-effects including respiratory depression, nausea, bradycardia and constipation and long-term use of opiates can cause addiction [2]. 

Analgesic Plants Opioid Opium poppy, myrrh... 

Analgesic Plants Opium Poppy History and Botany... 

During the nineteenth century, chemists had a good deal of success in isolating and purifying natural products from plant sources. Morphine was isolated as a pure compound from crude opium in 1804. Quinine was isolated from the bark of the cinchona tree in 1820 and was initially employed as a fever reducer. However, its effectiveness against malaria was soon discovered and it found an alternative highly important medical use. Sodium salicylate was isolated from the bark of the willow tree in 1821 and was also shown to have analgesic, antipyretic, and antiinflammatory properties. It took an additional 76 years, until 1897, to synthesize the acetyl derivative, acetylsalicyclic acid, commonly known as aspirin. 

Narcotic analgesics Morphine and many of its homologues, when administered in medicinal doses, relieve pain and produce sleep. In poisonous doses, these produce stupor, coma, convulsions and ultimately death. Morphine narcotics are sometimes referred to as opiates, since they are obtained from the opium poppy. 

Morphine is the major alkaloid in opium, the dried latex obtained from the opium poppy, Papaver somniferum. About 25% of the mass of opium is composed of alkaloids, with morphine constituting about 12-15%. Morphine is a powerful analgesic, and remains one of the most valuable for relief of severe pain. However, most of the morphine extracted from opium is processed further to give a range of semi-synthetic drugs, with enhanced or improved properties. A means of extracting morphine from the other alkaloids in opium is thus desirable. 

Both morphine and codeine are valuable analgesics. Morphine is extracted from opium, the dried latex of the opium poppy, and codeine is usually obtained from morphine by semi-synthesis (see Box 6.2), since the amounts in opium are rather small. Thebaine is a valuable raw material for semi-synthesis of a wide range of morphine-like drugs. 

In the past, a number of discoveries have been made in the absence of any knowledge about the receptors or ligands. One of the earliest examples of this kind is morphine (65) which was used for many years as an analgesic agent (as a constituent of opium, extracted from the poppy plant, Papaver somniferum) without... 

Opium alkaloids [Codeine (12), Morphine (13)] Papaver somniferum L. (opium poppy) Antitussive Narcotic analgesic... 

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