Papaverine from Papaver somniferum

The opiate alkaloid, papaverine, from Papaver somniferum is an anti-spasmodic, vasodilator, and smooth muscle relaxant. Its total synthesis has been studied since Pictet and Gams early work in 1909 and has since been followed up by various industrial syntheses up till the early 1950s using important industrial commodities as vanillin, acetovanillone, veratraldehyde (methylvanillin), and homoveratric acid as starting materials (see Figure 4.50). Table 4.23 summarizes the results of the five synthetic plans for this natural product. All are convergent... 

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). 

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). 

Papaverine Papaverine, molecular formula C20H21NO4, is an isoquinoline alkaloid isolated from poppy seeds Papaver somniferum, family Papaveraceae). This alkaloid is used mainly in the treatment of spasms and of erectile dysfunction. It is also used as a cerebral and coronary vasodilator. Papaverine may be used as a smooth muscle relaxant in microsurgery. In pharmaceutical preparations, papaverine is used in its salt form, e.g. hydrochloride, codecarboxylate, adenylate and teprosylate. The usual side-effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, increased transaminase levels, hyperbihr-unemia and vertigo. 

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... 

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. 

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). 

We switch to a completely different kind of alkaloid made from a different kind of amino acid. The benzyl isoquinoline alkaloids have a benzyl group attached to position 2 of an isoquinoline ring. Usually the alkaloids are oxygenated on the benzene ring and many are found in opium poppies (Papaver somniferum). For all these reasons papaverine is an ideal example. 

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 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). 

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. 

There are also many alkaloids based on isoquinohne, but fewer on quinoline nuclei papaverine and morphine from the opium poppy Papaver somniferum) and quinine (Cinchona officinalis) are typical. 

Papaverine and other benzylisoquinoline alkaloids have been isolated from Russian Kirghiz opium.70 Examination of opium samples from various localities in Korea has revealed that papaverine content does not vary from area to area.71 Four species of Papaveraceae have been examined for relative amounts of papaverine and other alkaloids in different segments of plant tissue.72 A study of the variation with time of papaverine content in the germinating seedling of Papaver somniferum has been reported.73... 

Opium, Gum opium crude opium. Air-dried, milky exudation from incised, unripe capsules of Papaver somniferum L., Or jP. album Mill., Papaveraceae. Habit of the plant Asia Minor, Persia, China, Africa, India cultivated in tlie Balkan States, Hungary, Southern Russia. In Japan the strain cultivated from the production of opium is called Ikkanshu Appearance and sources Chem. A Eng. News 32, 2701 (1954). Conshf, About 20 alkaloids, constituting about 25% of the opium meconic acid, some lactic and sulfuric acids, sugar, resinous and waxy-like subsrances 12 25% water. Morphine is the most important alkaloid and occurs to the extent of 10-16%, noscapine 4-8%, codeine 0 8-2.5%, papaverine 0 5 2,5%, thebaine 0,5-2%,... 

Colchicum cornigerum on the basis of an X-ray analysis of its methiodide. A review on the opium poppy Papaver somniferum describing its diverse uses and effects has appeared.Apparently the positive identification of morphine, codeine, thebaine, papaverine, and narcotine in unknown resins and powders may be taken as evidence that they are derived from P. somniferum. The yield and alkaloid content of P. somniferum capsules upon fertilization has been determined. ... 

There is some evidence that the production of the minor alkaloids, such as narcotine and papaverine, is more dependent upon locality. Narcotine has been reported as absent from opium produced in France and to be particularly abundant (up to 7-11%) in that from Japan (139). It is present in opium from most of the usual sources derived from Papaver somniferum var. album, and it is absent from the latex of P. somniferum var. nigrum. It is possible that in this instance the locality difference is due to difference of strain. The presence or absence of papaverine, on the other hand, is said to be determined by locality in samples all derived from var. album. It has been found in samples from Asia Minor, China, America, France, Persia, and Egypt, and not in those from Bengal, Patna, and Benares. It is, of course, possible, though not in any way proved, that local strains may have been developed in these diverse sites. 

The Juice opium in Greek) or latex from the unripe seed pods of the poppy Papaver somniferum is among the oldest recorded medications used by humans. The writings of Theophrastus around 200 BC describe the use of opium in medicine however, evidence suggests that opium was used in the Sumerian culture as early as 3500 BC. The initial use of opium was as a tonic, or it was smoked. The pharmacist Surturner first isolated an alkaloid from opium in 1803. He named the alkaloid morphine, after Morpheus, the Greek god of dreams. Codeine, thebaine, and papaverine are other medically important alkaloids that were later isolated from the latex of opium poppies. 

Papaverine usually occurs to the extent of 0.5 to 1 % in opium (1) and was isolated from the mother liquors of the morphine extraction in 1848 (2). It is found in all parts of Papaver somniferum L. (var. album), especially in... 

Narcotine has been found only in opium or in the source plant, Papaver somniferum L., the content in opium being of the order of 0.7 to 6.4% (95-98), although some Persian opium may contain as much as 11.2 % (99), while a Chinese variety of P. somniferum is stated to be devoid of this alkaloid (100) as well as of papaverine. The seeds contain detectable amounts of the alkaloid, and the content in the dried plant is from 0.008 to 0.276 % (101) and depends upon the state of maturity of the plant. The reported presence of narcotine in a number of fruits and vegetables and its confusion with vitamin C are erroneous, or at best unconfirmed (102-106). 

Opioids are those substances that can activate localized opioid receptors in the pain-controlling system of the body. Their action can therefore be antagonized by naloxone. From a clinical point of view, morphine is the most important substance of this group. It is obtained from opium, which is the brownish latex obtained from cuts made in the unripe but fully grown fruits of Papaver somniferum, the opium poppy. Opium contains not only morphine but also over thirty other alkaloids (Fig. 8-13) including the isoquinoline alkaloids codeine, papaverine, noscapine, thebaine and others, which make up ca. 25% of the opium. The alkaloids in opium are sometimes present as salts of meconic acid. The opiates form a separate subgroup within the opioids whose member... 

Indian opium (from Papaver somniferum) contains more than 30 different isoquinoline alkaloids (22 %), which can be divided into those of a morphine type and those ofa papaverine type (Fig. 5.49). The main alkaloids are morphine (Greek Morpheus God of dreams), arormd 12 %, and narcotine, around 5 %. The remainder comprises meconic acid (11 %), water (14 %), sulfuric and lactic acid (8%), fats, proteins, sugars and waxes (ca. 44%). [72, 81]... 

Laudanosine or Af-methyltetrahydropapaverine is a recognized metabolite of atracurium and cisatracurium. Laudanosine decreases the seizure threshold, and thus, it can induce seizures if present at sufficient threshold concentrations however, such concentrations are unlikely to be produced consequent to chemodegradable metabolism of clinically admiiustered doses of cisatracurium or atracurium. Laudanosine also occurs naturally in minute amounts (0.1 %) in opium, from which it was first isolated in 1871. Partial dehydrogenation of laudanosine will lead to papaverine, the alkaloid found in the opium poppy plant (Papaver somniferum). Laudanosine is a benzyltetrahydroisoquinoline alkaloid. It has been shown to interact with GABA receptors, opioid receptors, and ificotinic acetylcholine receptors, but not benzodiazepinergic or muscarinic receptors which are also involved in epilepsy and other types of seizures. 

The opiate alkaloids are a mix of semisynthetic and synthetic compounds derived from or related to the extract of the unripe seed pods of the opium poppy Papaver somniferum. Specifically, the alkaloids are obtained from the latex, or milky, exudates of the seed pod that appear when it is cut or sliced. The liquid contains about 10% morphine and about 1.5% codeine, with various amoimts ( 0.2-8%) of papaverine, thebaine, and noscapine (Table 8.3). The... 

Employing labeled A-norlaudanosolines it has been shown that it is the precursor of papaverine, the hydrophenanthrene alkaloids (IIB), and reticuline (203) in Papaver somniferum. Laudanosoline itself was found to be incorporated into berberine in Berberis japonica, the carbon atom 8 of the latter base originating from the A-methyl group of the former (198). 

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