Opium alkaloids papaverine

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. ... 

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. 

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. 

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. 

Papaverine is an opium alkaloid initially isolated in the mid-1800s. It relaxes smooth muscle and is a potent vasodilator. As such it is used to dilate pulmonary and other arteries. It is therefore sometimes of use in the treatment of angina pectoris (usually caused by partial blockage of the coronary artery), heart attacks and bronchial spasms. 

Opium alkaloids are nonpeptide agonists for the opioid peptide hormone receptors. The dried latex of Papaver somniferum (opium), or the seed capsule of the plant itself, are the sources of almost 25 alkaloids. Some simple isoquinolines from opium, like papaverine (5.86), are antispasmodics. The principal alkaloid ( 10% of the total) is morphine (3.11), which is also an isoquinoline (rings C and E) but can addihonally be considered a phenanthrene derivahve (rings A, B, and C). 

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, 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... 

The results obtained from a comparison of the toxic properties of some opium alkaloids, including papaverine, were reported by Drommond et al. (58) and Aurousseau and Navarro (59). Papaverine is rather toxic to albino rats irrespective of age and sex and has a low toxicity to some bacteria (58). Subcutaneously administered papaverine is less toxic than that given per os (59). 

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.]...

Papaverine is a commonly known opium alkaloid that is a smooth muscle relaxant and is used as a coronary vasodilator [2]. Scheme 5 shows the synthetic route to papaverine proposed by Pictet and Gams [21] almost a century ago [2]. 

Opium contains many alkaloids, but the only important ones are morphine (10%) and codeine papaverine is occasionally used as a vasodilator (see p. 546). Purified preparations of mixtures of opium alkaloids, e.g. papaveretum (Omnopon), are available minus noscapine which is suspected of genotoxicity. 

Papaverine is an alkaloid present in opium, although it is not related chemically or pharmacologically to other opium alkaloids. It has a direct relaxant effect on smooth muscle, partly attributable to inhibition of phosphodiesterase. 

Treatment of papaverine (C20H21O4N, one of the opium alkaloids) with hot concentrated hydriodic acid yields CH.J, indicating the presence of the methoxyl group —OCH3. When 4.24 mg of papaverine is treated with hydriodic acid and the CH3I thus formed is passed into alcoholic silver nitrate, 11.62 mg of silver iodide is obtained. 

II. The stmctuie of papaverine, C2oH2i04N, one of the opium alkaloids, has been established by the following synthesis ... 

Two basic types of structures arc recognized among the opium alkaloids, the plmnanthreite (morphine) type and the benzylisoqtiinoline (papaverine) type (.see structures). 

Trade names Angioverin Genabid Optenyl Pameion Papaverine 60 Papaverini Pavabid Pavagen Pavased Pavatine Indications Peripheral and cerebral ischemia Category Opium alkaloid Vasodilator, peripheral Half-life 0.5-2 hours... 

For the identification of a number of opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine, cryptopine, narceine) and heroin, 3-0-acetylmorphine, 6-0-acetylmorphine and acetyl codeine, Viala et al. 7 made use of three gas chromatographic columns of different polarities (SE-30 3 %, OV-1 2 % and OV-1 2 % plus Igepal 0.2 %).They obtained reliable separation and identification in this way, which was based on the difference in the retention times in the three columns. 

Lurie analyzed drugs of forensic interest on octadecyl columns with 0.005 M 1-heptane-sulfonic acid in methanol - water - acetic acid (40 59 l)(pH 3.5) (Table 7.3). The system enabled a simultaneous analysis of acidic, neutral and basic drugs. Among the compounds analyzed were the opium alkaloids (Fig. 7.11). A similar system was applied for the analysis of papaverine in plasma8. ... 

Fig. 7.4. Separation of some opium alkaloids-Column Nucleosil 10C18 (300x4 mm ID), mobile phase (65 35), flow rate 1.5 ml/min. Peaks 1, morphine 5, papaverine 6, noscapine.

The opium poppy contains four alkaloids papaverine, morphine, codeine and noscapine (=narcotine), with four areas of therapeutic use ... 

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