Opium alkaloids codeine

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

Natural opium alkaloids codeine phosphate hydromorphone hydrochloride morphine hydrochloride morphine sulfate oxycodone hydrochloride oxymorphone hydrochloride... 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

Codein phosphate and hydrochloride caused contact dermatitis in a worker in the production of opium alkaloids. Codeine bitartrate caused contact dermatitis in a worker in the production of concentrated poppy straw. Codeine was a sensitizer in a laboratory worker at an opiate-manufacturing pharmaceutical company, also sensitive to thebaine. 

Estimation of Other Alkaloids in Opium. Of the other alkaloids the most important is codeine, and processes for its estimation in opium have been described by Cespari, Andrews,and Annett and co-workers methods for its assay in admixture with other drugs in tablets and other products are also available. The estimation of papaverine has been described by Issekutz,i and of narcotine by Snesarov. As to methods for the separation and estimation of two or more of these subsidiary alkaloids, codeine and narcotine have been dealt with by van der Widen,narcotine and papaverine by Annett and Bose, ( and the bromination of codeine and narceine has been studied by Vaisberg et al. with a view to estimation by this means. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

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. ... 

Neopine, C gHaiOgN. This alkaloid was discovered by T. and H. Smith in the final mother liquors obtained in the extraction of opium alkaloids, and was examined by Dobbie and Lauder, and later by van Duin, Robinson and Smith, who cystallised the base, found it isomeric with codeine and showed that it is jS-codeine (p. 251). The base crystallises from light petroleum in needles, m.p. 127-127-5°. In aqueous solution... 

A characteristic feature of the action of the opium alkaloids is their simultaneous depressing and exciting action on the central nervous system. In this respect there is no clear line of demarcation between the morphine group—morphine, codeine and thebaine—and the papaverine-narcotine group, and as the series is ascended in the order, morphine, papaverine, codeine, narcotine, thebaine, narcotic action diminishes and power of rellex stimulation increases until in thebaine a strychnine-like effect is exhibited. 

Opium alkaloids (morphine, codeine), acetylmorphine, oxyco-deinone, brucine, phenylbutazone, ketazone, trimethazone... 

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. 

More than 30 alkaloids have been identified in opium (Robbers et al. 1996). The most relevant are morphine (4-21%), codeine (0.8-2.5%), noscapine (4-8%), papaverine (0.5-2.5%), and thebaine (0.5-2%) (figure 8.4). Other opium alkaloids include narceine, protopine, laudanine, codamine, cytopine, lanthopine, and meconidine. Numerous other opioids have been synthesized from opium alkaloids. Among them is heroin, or diacetylmorphine. 

Agonists include natural alkaloids of opium (morphine, codeine, and a large blend of natural alkaloids, pantopon, and omnopon), their analogs (hydrocodon and hydromor-phone, oxycodone, and oxymorphone), derivatives of morphinane (levorphanol), and a number of synthetic compounds derivatives of phenylpiperidine (meperidine, promedol), 4-anilidopiperidines (fentanyl, sufentanyl, alfentanil), and derivatives of diphenylheptane (methadone, propoxyphene). 

The most widely used agonists in medical practice are the opium alkaloids morphine and codeine. However, semisynthetic derivatives (hydromorphone, oxymorphone, hydrycodon, oxycodone), whose use is even preferred in certain cases, and strong, purely synthetic compounds (methadone, meperidin, fentanyl, sufentanyl, and others) have found wide use. 

Capillary electrophoresis is suitable for use to separate a wide spectrum of both large and small biological molecules. This method was used for analysis of opium alkaloids such as thebanine, codeine, morphine, papaverine and narcotine. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

The most important other opium alkaloid is codeine. In contrast to morphine, codeine has a high oral-parenteral potency ratio due to less first-pass metabolism. Codeine is considered a prodrug, since it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide. Approximately 10% is demethylated to morphine. The analgesic effect of codeine is due to the formation of these metabolites as codeine itself has a very low affinity for opioid receptors. The half-life of codeine in plasma is 2 hours. 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

Codeine, which is an opium alkaloid is most commonly opiate used as antitussive and more selective for cough centre. Like morphine, it depresses cough centre but is less constipating and abuse liability is low. It is relatively safe drug used in cough along with analgesic property and it s only important adverse effect is constipation. 

Opium alkaloids and derived phenanthrene alkaloids codeine, morphine, (Avinza, Kadian, MSContin, Roxanol), hydromorphone (Dilaudid), oxymorphone (Numorphan), oxycodone (dihydroxycodeinone, a component of Oxycotin, Oxydose, Oxyfast, Percodan, Percocet, Roxicodone, Tylox)... 

Or they may be grouped according to the genus of their plant source (morphine and codeine, Section 23-2, are examples of opium alkaloids), or by their physiological effects (antimicrobials, antibiotics, analgesics), or by similarities in the route by which they are synthesized by the organism (biosynthesis). The structural and biosynthetic classifications make the most sense to the chemist and is the organization chosen here. 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Papaveretum is a mixture of purified opium alkaloids, as their hydrochlorides, and is now formulated to contain only morphine (85.5%), codeine (7.8%), and papaverine (6.7%). It is used for pain relief during operations. 

The opium alkaloids morphine, codeine, and thebaine have a phenanthrene nucleus (Figure 11.10 and Figure 11.11). 

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. 

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... 

Janicot et al. presented the separation of opium alkaloids using sub-critical and supercritical fluid chromatography [20]. Carbon dioxide-meth-anol-triethylamine-water mixtures were used as the mobile phase with packed aminopropyl or bare silica columns. The influence of aminated polar modifiers such as methylamine, ethylamine, and triethylamine was studied. Figure 7.15 shows the separation of six opium alkaloids narcotine, papaverine, thebaine, codeine, cryptopine, and morphine on a Lichrosorb Si-60 column. The method gave comparable results with HPLC. 

Figure 7.15 Separations of opium alkaloids on bare silica. Column = x 0.46 cm ID stationary phase, 5-/im LiChrosorb Si-60 silica mobile phase, carbon dioxide-methanol-methylamine-water (83.37 16.2 0.15 0.23, w/w) Solutes 1, narcotine 2, papaverine 3, thebaine 4, codeine 5, crytopine 6, morphine. [Reprinted from Ref.20, J. Chromatogr. 437, 351 (1988) with kind permission of Elsevier Science Publishers, The Nether-, lands.]...

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