Morphine opium derivative

Morphinans (compactly fused Phe, C6, C5N, C6 and C40 rings) Codeine (opium-derived addictive, analgesic, antitussive, spasmolytic narcotic) morphine (opium-derived addictive, analgesic, antitussive, sedative, spasmolytic narcotic heroin is the semisynthetic diacetate) thebaine (non-analgesic, toxic, convulsant narcotic and semi-synthesis precursor of the anti-addiction drug naltrexone). 

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. 

Opium derivatives, such as morphine and codeine phosphate, have been used for a iong time, but the piperidine derivatives loperamide (Imodium) and diphenoxylate (Lomotii) are now preferred. Both are p-receptor agonists, iargeiy devoid of centrai opiate-iike effects, and reiativeiy insoiubie in water, so that parenterai use and abuse are aimost impossibie. 

The alkaloids derived from opium are collectively known as opiates. Morphine, codeine, and thebaine are well-known opium derivatives. Paregoric is an opium tincture (opium in an alcohol mixture). 

Both raw and cooked opium contain alkaloids. These alkaloids can be extracted from the opium to produce opium derivatives for legal pharmaceuticals or for illegal consumption, such as morphine and heroin. The morphine alkaloid content, which ranges from 8% to 12%, determines the quality of the opium... 

Many opium-derived and other IQs are psychoactive, the best known being the analgesic, addictive, narcotic, opium-derived morphinan alkaloids codeine and morphine (heroin being the semi-synthetic diacetate of morphine). The tertiary or quaternary amine structural component is important for the activity of some Erytkrina alkaloids and bisbenzyliso-quinolines (notably the major curare component (+)-tubocurarine) as antagonists of the nACh-R involved in neuronal excitation of skeletal muscle. The planar disposition of some polycyclic benzophenanthridines enables intercalation (parallel interleaving) between the base pairs of DNA. A variety of naturally occurring and synthetic IQ compounds are protein kinase inhibitors. 

Morphine A derivative of opium best known as a potent pain-relieving medication (Chapter 2). 

There are two possible biosynthetic pathways for the conversion of thebaine to morphine, Fig. (67) [148]. One is orthodoxically known in the litreatures [4, 130, 131], that is morphine biosynthesis from thebaine via codeinone and codeine. Another one i.e. the first ever demonstrated by Brochmann-Hanssen in 1984 [149], is the biosynthesis via oripavine and morphinone. The transformed clone could synthesize codeine but lacked morphine though the non-transformed clone obtained from the same plant material accumulated morphine at the latter developmental stage (Table 21). This suppressed morphine content was also observed in the opium derived from the transformed P. somniferum plants that had been... 

Morphins and derivatives A -methylpiperazine Oils, vegetable and animal medicinal grade—refined and concentrated Opium derivatives Ox bile salts and derivatives bulk, uncompounded Penicillin bulk, uncompounded Physostigmine and derivatives Pituitary gland derivatives bulk, uncompounded Procaine and derivatives bulk, uncompounded Quinine and derivatives Reserpines... 

Another summary with special reference to the chemical structure of opium derivatives and allied synthetic substances and their pharmacodynamic action is supplement No. 138 to the Public Health Reports of the U.S. Public Health Service entitled Studies on Drug Addiction and pubUshed in 1938 (2). Synthetic analgesics have been considered subsequently in many review s. Extensively consulted in the preparation of this article were the reviews by Fellows and Ullyot (3), Lee (4), Wikler (5), Isbell and Fraser (6), Beckett (7), Schaumann (8), and Schoen (9). This review will mainly be concerned with analgesia, addiction, and fate, of morphine and related analgesics. 

Codeine and morphine, narcotics derived from opium. 

Poppy extracts have been the source of pain relief and euphoria for thousands of years. Opium derivatives, such as morphine and codeine, are the most effective analgesics available, and they have a wide variety of uses as well as potentially serious side effects. Recognition of the variability of receptor response and metabolism can help to explain the wide range of responses to the same dose of medications, and perhaps also explain why some people become addicted and others do not. 

Methadone is a potent synthetic opioid analgesic, structurally unrelated to any of the opium-derived alkaloids. It is a highly lipophilic, basic drug (pKa 9.2) available as a hydrochloride powder formulation that can be reconstituted for oral, rectal, or parenteral administration. Methadone was developed in Germany in 1942 as a synthetic substitute for morphine, and has been approved and widely employed for opioid detoxification maintenance as well as acute and chronic pain management. 

The class of narcotic drugs encompasses the opium-derived drugs of morphine, heroin, and codeine (Figure 16.1) as well as other narcotics, such as meperidine, hydromorphone, hydrocodone, and the fentanyl compounds. Because these are highly polar compounds and often require high temperatures for elution, GC is difficult and often demands derivatization. Morphine, for example, because of its amphoteric nature, is not only difficult to extract but must be derivatized to obtain good quantitative data. 

Opioids and morphine derivatives Fentanyl, Codeine, Heroin, Morphine, Opium, Methadone, Oxycodone, HCL... 

The Opiates. The International Narcotics Control Board—Vienna, tracks the tick production of narcotic dmgs and annually estimates world requkements for the United Nations. Thek most recent pubHcation (100) points out that more than 95% of the opium for Hcit medical and scientific purposes is produced by India and, in a declining trend, only about 600 t was utilized in 1988. This trend appears to be due to the fact that the United States, the largest user of opium for alkaloid extraction, reduced the amount of opium being imported from about 440 t in 1986 to 249 t in 1987 and 224 t in 1988. The United States used about 48 t of morphine (2, R = H) in 1988, most (about 90%) being converted to codeine (2, R = CH3) and the remainder being used for oral adrninistration to the terminally ill (about 2 t) and for conversion to other materials of minor commercial import which, while clearly alkaloid-derived, are not naturally occurring. 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

Although morphine has been prepared by total synthesis, the complexity of the molecule makes such an approach unattractive on a commercial scale. The drug in fact is obtained by fractionation of opium obtained from the poppy morphine in turn is used as starting material for various derivatives. If it were not for the importance of these drugs in the clinic, some progress might have been made in eradication of the plant. 

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

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. 

In the strict sense, opiates are drugs which are derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non-peptidic structures. The old term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, pqrtidic or non-peptidic, that produces morphine-like effects through an action on opioid receptors. 

Rice, K.C. (1980) Synthetic Opium Alkaloids and Derivatives. A Short Total Synthesis of (ib)-Dihydrothebainone, ( )-Dihydrocodeinone, and ( )-Nordihydrocodemone as an Approach to a Practical Synthesis of Morphine, Codeine, and Congeners. Journal of Organic Chemistry, 45, 3135-3137. 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

Opiate A drug related to morphine, derived from opium. 

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]. 

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