Papaver somniferum, isoquinoline alkaloids

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. 

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. 

Strychnos usambarensis (Loganiaceae) [root] S. Am. Indian poison curare component Derived synthetically from morphine, a morphinan isoquinoline alkaloid from Papaver somniferum (opium poppy) (Papaveraceae) [aerial]... 

The benzylisoquinolines are formed from two molecules of fhe aromafic amino acid, tyrosine. In the past ten years, this pathway has been probed at the enzyme and gene level. The recent linking of the phloem-specific expression of tyrosine/Dopa decarboxylase (TYDC) genes with the bios)mthesis of the isoquinoline alkaloids in the opium poppy, Papaver somniferum (Facchini and De Luca, 1994, 1995, 2008 Liscombe and Facchini, 2008), and the association with alkaloid accumulation as part of the plant defence mechanism (Wink, 1993 Facchini et al, 1996) are of particular interest in furthering our knowledge of the location of alkaloid biosynthesis. 

The isoquinoline alkaloids include the analgesics morphine and codeine as well as the antibiotic berberine (Fig. la). Morphine and codeine are two of the most important analgesics used in medicine, and plants remain the main commercial source of the alkaloids (8). Development of plant cell cultures of Eschscholzia califomica, Papaver somniferum, and Coptis japonica has aided in the isolation and cloning of many enzymes involved in the biosynthesis of isoquinoline alkaloids (9). 

Transformation of Papaver somniferum L. and enhanced production of isoquinoline alkaloids... 

Comparatively few simple isoquinoline alkaloids have been found to occur naturally. Until now such compounds have been encountered in three or four species of the Cactaceae, in a Chenopodiaceae [Salsola arbuscula Pall. (S. richteri Karel)], in three species belonging to the family of the Fumari-aceae [Corydalis pallida (Thunb.) Pers.,C. awrea Willd., C. tvherosa DC.] and in one Papaveraceae Papaver somniferum L.). While no doubt exists as to the native occurrence of the anhalonium and salsola isoquinolines, hy-drohydrastinine and hydrocotarnine may have been artifacts from the benzylisoquinoline alkaloids of Corydalis tuberosa and Papaver somniferum. 

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... 

Alkaloids in mammals can be sequestered from vegetal or animal sources and are produced by the organism. It is known that morphine can be synthesized by mammalian cell from dopamine. This mammalian endogenous morphine is identical with vegetal morphine from Papaver somniferum It is empirically evidenced that human cells also can produce morphine. Exogenous alkaloids, depending on their bioactivities, can work in mammals in curative process of disorders and diseases and as hallucinogens or as poisons. Other mammalian alkaloids are well-known alkaloids such as beta-carbolines and isoquinolines. 

Fig. 2. Alkaloid biosynthetic pathways are associated with a diverse variety of cell types. The tissue-specific localization (shaded) of enzymes and/or gene transcripts are depicted for the biosynthesis of tropane alkaloids in Atropa belladonna and Hyoscyamus niger roots (A), monoterpenoid indole alkaloids in Catharanthus roseus leaves (B), pyrrolizidine alkaloids in Senecio vernalis roots (C), pyrrolizidine alkaloids in Eupatorium cannabinum roots (D), benzyl-isoquinoline alkaloids in Papaver somniferum vascular bundles (E), and protoberberine alkaloids in Thalictrwn flamtm roots (F).

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]... 

An example of this are the concentrations of the isoquinoline alkaloids morphine, codeine, and thebaine (D 22.1.2) in the latex of Papaver somniferum. Morphine concentrations peak in the morning codeine, at noon and thebaine gradually increases from 6 am until the late evening... 

The isoquinoline pathway s enzyme orthologs in other plants showed that genes of methyltransferase family such as (R,S)-reticuline 7-0-methyltransferase, coclaurine 4 -0-methyltransferase, (S)-norcoclaurine 6-0-methyltrasferase, columbamine 0-methyltransferase, coclaurine A-methyltransferase, putrescine A-methyltransferase responsible for the production of reticuline, coclaurine, norcoclaurine, columbaine have been reported from Papaver somniferum, Coptis japonica, Thalictrum flavum, Thalictrum tuberosum, Coffea liberica, Cojfea arabica, Cojfea canephora, Nicotiana tabacum. Solarium tuberosum. Datura stramonium, Hyoscyamus niger, and Atropa belladonna. Pathway contains information of about four alkaloids such as dopamine, colchicine, ephedrine, and methamphetamine and identified two missing links. 

The theme running through the present paper is that isoquinoline alkaloids have been both a boon and a curse to mankind. The cultivated opium poppy, Papaver somniferum, which appears to have originated several thousand years ago in the western Mediterranean region, has given rise to serious and large-scale social problems, but at the same time its dried juice, opium, has provided no less than five alkaloids — morphine, codeine, thebaine, papaverine, and noscapine (narcotine) — that are currently used in medicine. 

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