Hyoscyamin

M.p. 114-116 C. Prepared by racemization of hyoscyamine. It and its salts are used to dilate the pupil of the eye. Given internally they reduce the secretion of saliva and relieve spasmodic pains. 

Atropiae (41), isolated from the deadly nightshade Airopa belladonna L.) is the racemic form, as isolated, of (—)-hyoscyamine [which is not isolated, of course, from the same plant but is typically found ia solanaceous plants such as henbane (HyosQiamus mgerl. )]. Atropiae is used to dilate the pupil of the eye ia ocular inflammations and is available both as a parasympatholytic agent for relaxation of the intestinal tract and to suppress secretions of the saUvary, gastric, and respiratory tracts. In conjunction with other agents it is used as part of an antidote mixture for organophosphorus poisons (see Chemicals in war). 

Kutrase 29/100 amylase/pancrease /Hpase / ceUulase/hyoscyamine / phe Schwarz... 

Donnazyme 20/100 nyltoloxamine pancreatin/pepsin/homatropine/hyoscyamine/atropin Robins... 

Atropa Belladonna Linn. Leaves, 0-4 roots, 0-5 seeds, 0-8 whole plant, 0-2 to 1-0 h5mscyamine with some hyoscine atropine has been found but may have resulted from racemisation during extraction apoatropine and possibly belladonnine (Kreitmair Atropa bcetica. Leaves, 0-82-1-06 roots, 0-94 fruit, 1-09 hyoscyamine and atropine. 

Datura alba Nees. Pericarps, leaves, stems hyoscine. Seeds, hyoscine with a little hyoscyamine. 

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. 

Datura fastuosa. Variety niger fruits, 0-2 leaves and stems, 0-12 roots, 0-1. Variety Jlor ccerul. plen seeds, 0 25. Variety Jior alb. plen seeds, 0-22. In all three varieties, hyoscine alone, or with hyoscyamine. 

Datura Metel. Fruits, 0-12 leaves, 0-2 to 0-5 roots, 0-1 to 0-2 seeds, 0-2 to 0-5. Usually mainly hyoscine occasionally a little atropine or hyoscyamine. worHyoscyamine has also been found.No hyoscine (Libizov ). 

D. quercifolia. Leaves, 0-42 seeds, 0-29. Hyoscine and hyoscyamine (Kircher ). 

Duhoisia myoporoides. Yields of 3 per cent., mostly hyoscine, have been mentioned, but great variation in nature of alkaloidal content is on record, e.g., hyoscyamine, -hyoscyamine, hyoscine. Hyoscyamine and norhyoscyamine, but no hyoscine. Hyoscine or hyoscyamine or both. dZ-Hyoscine, tigloidine, valeroidine, poroidine and woporoidine present hyoscyamine and norhyoscyamine absent. The limits of these variations, at least as regards the two principal alkaloids, hyoscyamine and hyoscine, have probably been settled by Hills, Trautner and Rodwell, who confirmed the statement of Barnard and Finnemore that in the northern portion of the distribution area of this plant, it yields mainly hyoscine and in the southern section mainly hyoscyamine. In 54 samples of leaves from individual trees they found 0-9 to 4-0 total alkaloids in those from the northern section, with hyoscine as the chief component, and 1-0 to 2-7 from those of the southern section, with hyoscyamine replacing hyoscine. 

Ilyoscyamus albus. Leaves, 0-2 to 0-56 roots, OT to 0T4 seeds, 0-16 hyoscyamine and hyoscine. 

Hyoscyamus muticus. Leaves, 1-4 leaves and stems, 0-6 seeds, 0-9 to 1-34 stems, 0-6 hyoscyamine. ... 

Ilyoscyamus niger. Leaves, 0-045 to 0-08 roots, 0-16 seeds, 0-06 to 0-1 tops, 0-07 to 0-1. Chiefly hyoscyamine with some atropine and hyoscine cj. Sievers and Lowman, Allan. A historical account of this drug has been published by Hocking. ... 

Hyoscyamus reticulatus. Seeds, 0-08 whole plant, 0-12 to 0-24. A little hyoscyamine. ... 

Matidragora scopolice. Leaves and stems said to contain about 0-6 chiefly hyoscyamine. 

Mandragora vernalis. Hyoscyamine, hyoscine, -hyoscyamine, mandragorine (p. 83). ... 

Scopolia carniolica S. atropoides, S. Hladnikiana). Rhizomes, 0-43 to 0-51 hyoscyamine and hyoscine. ... 

Scopolia japonica. Leaves, 0-18 hyoscyamine and norhyoscj mine. ... 

Scopolia lurida (Anisodus luridus). Roots, 2 to 2-8, of which about one-fifth is hyoscine (Kreier ). According to Rabinovich and Konovalova, the root contains hyoscyamine and cuscohygrine (p. 103) but no hyoscine. ... 

Solandra Iccvis Hook, S, longifiora Tussac), 0-16 norhyoscyamine, noratropine, hyoscyamine, atropine (Petrie). ... 

The British Pharmacopoeia (1932) recognises three of these solanaceous drugs and specifies for them minimum requirements per cent, of total alkaloids, calculated as hyoscyamine, viz. belladonna, leaves 0-3, root 0-4 henbane, leaves and flowering tops 0-05 stramonium, leaves and flowering tops 0-25. The United States Pharmacopoeia, XIII, specifies the same minimum limits for belladonna leaves and stramonium and for henbane, 0-04. 

Hyoscyamine, Ci,H2303N. This, the most commonly occurring alkaloid of the oup, was obtained by Geiger and Hesse from henbane. Ks hydrolysis into a base and an acid was observed by Hohn and Reichardt. The accepted, empirical formula is due to Ladenburg, who s owed that it was a physical isomeride of atropine. Hyoscyamine... 

Hyoscyamine is readily converted into the dZ-form, atropine, by melting or by the addition of small quantities of caustic alkali to its cold alcoholic solution. The same change is brought about by sodium carbonate or ammonia. ... 

When heated with acids or alkalis, hyoscyamine undergoes hydrolysis into tropine and dZ-tropic acid probably via conversion into atropine, and it is this alkaloid which is hydrolysed. According to Gadamer, when hyoscyamine is hydrolysed with cold water the products are inactive tropine and Z-tropie acid. Amenomiya has shown that Ladenburg and Hundt s partially synthetic d- and Z-atropines were probably mixtures of atropine with d- and Z-hyoscyamines. He resolved dZ-tropic acid into the d- and Z- forms, esterified these with tropine in 5 per cent, hydrochloric acid, and so obtained d- and Z-hyoscyamines, the latter identical with the natural alkaloid, d- and Z-Hyoscyamines have also been obtained by Barroweliff and Tutin by the resolution of atropine by means of d-camphorsulphonic acid. 

This synthetic tropidine was converted into bromodihydrotropidine by hydrogen bromide in aeetie aeid, and the solution heated with 10 per cent, sulphurie acid at 200-10°, when it passed into -tropine,and, sinee this may be partially converted into tropine by oxidation to tropinone and reduction of the latter by zinc dust and hydriodic acid, this series of reactions affords a complete synthesis of tropine and of the tropeines. Combining the formula given above for tropine with that of tropic acid, atropine and hyoscyamine are represented as follows ... 

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The alkaloid may be separated from accompanying hyoscyamine by extracting most of it with ether and then crystallising the mixed oxalates from water, that of norhyoscyamine separating first. It crystallises in colourless prisms, m.p. 140°, [a]j, — 23-0° (50 per cent. EtOH), is soluble in alcohol or chloroform, less so in ether or acetone, and sparingly in water... 

Hyoscine (Scopolamine, Atroscine), Ci,H2i04N. The name hyoscine was first used by Hohn and Reichardt for the basie hydrolytic product of hyoscyamine, now known as tropine. It was subsequently used by Ladenburg for a supposed isomeridc of atropine, Cj HjgOjN, isolated from the mother liquors of hyoscyamine. This was found by Schmidt, Hesse and others to be identical with scopolamine, Ci,H2i04N, obtained by Schmidt from Scopolia japonica. The name hyoscine has priority and is in use, but scopolamine is also employed, especially in Germany. 

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. 

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