Datura alkaloids

Chapter 6 Datura Alkaloids Hyoscyamine and Atropine C17H2303N M.W. 289... 

At this writing anticholinergic agents are not widely used for the symptomatic treatment of asthma, although compounds such as atropine [51 -55-8] C17H23NO3, (18) have been used for centuries (111). Inhalation of the smoke produced by burning herbal mixtures, such as Datura Stramonium provided bronchodilation and rehef from some of the symptoms of asthma. The major active component in these preparations was atropine or other closely related alkaloids (qv). 

Datura arborea. Leaves, 0-44 seeds, 0-23 hyoscine with some hyoscyamine in young stems and roots (Kircher Roots, 0-16 leaves, 0-15 flowers or seeds, 0-12 alkaloid described as datu ine (Montesinos which should be atropine. 

The alkaloid can usually be obtained from the mother liquors of hyoscyamine, but Datura Metel, in which hyoscine is the chief constituent, was the better primary source but may now prove less valuable than selected Duboisia spp. (p. 66). A process of manufacture has been described by Chemnitius, and a method for the recovery of 1-hyoscine from racemised base by Schukina et al. A method for its estimation in presence of opium alkaloids has been devised bj Wallen and Callback. 

It may be noted that Datura Metel, in which hyoscine is usually the predominant alkaloid, has been recorded in one instance by Libizov as containing hyoscyamine, but no hyoscine, and a similar difference is mentioned for Scopolia lurida. ... 

Biosynthesis of tropan alkaloids hyosciamine and scopolamine by isomerization of alkaloid littorine in Datura. stramonium and related species 98CSR207. 

Figure 5.49 shows the four HOHAHA spectra obtained at 20, 40, 60, and 100 ms of hyocyamine, an alkaloid isolated from Datura fastusa. The various short-range and long-range homonuclear connectivities established on the basis of HOHAHA spectra of hyoscyamine provided a powerful tool for structure elucidation. The spectrum obtained with a mixing time of... 

Figure 5.50 (A) ID H-NMR spectrum of hyoscyamine, an alkaloid isolated from Datura fastusa. (B) HOHAHA spectra of the same compound recorded at 20, 60, and 100 ms. The projection spectra are taken at (a) 8 1.30, (b) 8 3.50, and (c) 8 5.16.

The earlier alkaloid literature contains numerous reports of studies aimed at discovering the existence of chemotypes involving these pharmacologically important compounds. An example of this sort of study comes from the work of Karnick and Saxena (1970) who were interested in the effect of elevation on total alkaloid content of Datura metel L. (Solanaceae), an important source of hyoscyamine [26]... 

Table 2.12 Alkaloid variation with elevation in Datura metel (from Karnick and Saxena, 1970)...

The family Solanaceae consists of about 85 genera and 2800 species of plants, of which, 80 are of medicinal value in the Asia-Pacific region. Solanaceaeare well known for their parasympatholytic tropane alkaloids, such as hyoscyamine. Classic examples are Atropa belladonna L. (belladona herb, British Pharmacopoeia 1963), Datura stramonium L. (stramonium, British Pharmacopoeia, 1963), and the dried leaves and flowering tops of Hyoscyamus... 

Like plasma and urine, matrixes from plant or environmental sources contain a vast diversity of components. Thus, achiral-chiral LC-LC is also useful for analysis involving samples from these sources. Stalcup et al. (1991) studied the enantiomeric purity of scopolamine extracted from Datura sanguinea in both homogenized plant leaves and commercial extracts. A reverse-phase separation on a C j g column separated the scopolamine from other alkaloid and matrix components while the enantiomeric separation (also in the reverse-phase mode) was carried out on two coupled [3-cyclodextrin columns or a single acetylated (3-cyclodextrin column. The single... 

The cholinergic hallucinogens all have common chemical constituents that are responsible for their pharmacological effects (Robbers et al. 1996). These are the tropane alkaloids hyoscyamine, scopolamine (or hyoscine), and atropine (figure 9.16). It is scopolamine, and not atropine or hyoscyamine, which primarily produces the central and hallucinogenic effects because it is the only one that passes the blood-brain barrier sufficiently. However, all three have peripheral effects. Datura stramonium contains 0.1-0.65% tropane alkaloids, which is principally... 

Toxicity from tropane alkaloids often results from their effects on autonomic function. Several species of Datura are freely available, either growing in the wild or cultivated as ornamental plants, such as angel s trumpet (Datura sauveolens). Periodic outbreaks of jimsonweed use occur, when adolescents learn about the psychoactive effects of the plant and intentionally ingest it. 

Other plants of the nightshade family, including Atropa belladonna (deadly nightshade), Hyoscyamus niger (black henbane), and Datura stramonium (Jimson weed), contain atropine-like toxins that are anticholinergic, blocking the muscarinic receptors. An incidence in southern Utah of cattle poisoned on black henbane, with many death losses, was recently reported (Pfister, 2003). Atropine and atropine-like alkaloids are discussed Section 2.2.1.7. 

Figure 2.14 Two common tropane alkaloids in Solanum spp. (a) atropine Datura), and (b) cocaine (Erythroxylon coca).

The tropane alkaloids (—)-hyoscyamine and (—)-hyoscine are found in the toxic plants deadly nightshade (Atropa belladonna) and thornapple (Datura stramonium) and are widely used in medicine. Hyoscyamine, usually in the form of its racemate atropine, is used to dilate the pupil of the eye, and hyoscine is employed to control motion sickness. Both alkaloids are esters of (—)-tropic acid. 

The base-catalysed racemization of the alkaloid (-)-hy oscy amine to ( )-hyoscyamine (atropine) is an example of enolate anion participation. Alkaloids are normally extracted from plants by using base, thus liberating the free alkaloid bases from salt combinations. (—)-Hyoscyamine is found in belladonna Atropa belladonna) and stramonium Datura stramonium) and is used medicinally as an anticholinergic. It competes with acetylcholine for the muscarinic site of the parasympathetic nervous system, thus preventing the passage of nerve impulses. However, with careless extraction using too much base the product isolated is atropine, which has only half the biological activity of (—)-hyoscyamine, since the enantiomer (+)-hyoscyamine is essentially inactive. 

A. Alkaloids 1. Belladonna-type solanaceous tropane alkaloids [Atropine (1), (—)-Hyoscyamine (2), Scopolamine ((—)-Hysoscine)(3)] Atropa belladonna L. (belladonna), Datura metel L., D. stramonium L. (jimson weed), Hyoscyamus niger L. (henbane), Mandragora officinarum L. (European mandrake), and other solanaceous species Anticholinergics (parasympatholytics)... 

Certain plants of the family Solanaceae, such as Atropa belladonna L., Hyoscyamus niger L., and Datura stramonium L., have been used medicinally for centuries in Europe because they contain tropane-type alkaloids.For example, atropine (1) [a racemic mixture of (+)- and (—)-hyoscyamine (2)] and (-)-hyoscyamine are competitive antagonists at the muscarinic acetylcholine receptor site, leading to antispasmodic and antiallergic effects. Scopolamine [(—)-hyoscine)] (3) is used in a transdermal patch for the prevention of motion sickness. Since these tropane alkaloids penetrate the blood-brain barrier, they also have psychoactive effects. ... 

Robins, R. J., Parr, A. J. and Walton, N. J. 1991. Studies on the biosynthesis of tropane alkaloids in Datura stramonium L. transformed root cultures. 2. on the relative contributions of L-arginine and L-ornithine to the formation of the tropane ring. Planta, 183 196-201. 

Atropine and scopolamine, the main toxic alkaloids of Datura stramonium and Datura ferox, were detected and quantified using HPLC-ESl-MS both in Datura seeds and in the gastric content of a man whose death was ascribed to a fatal heart attack [100]. 

Plants containing indoleamines include Psilocybe mushrooms, morning glory and Virola. Plants containing tropane alkaloids such as the muscarinic antagonists scopolamine and atropine are found in some members of the Solanaceae plant family—including datura, mandrake, henbane and... 

---