Atropina (U. S. P.)—Atropine.
Related entries: Belladonna.—Belladonna - Atropinae Sulphas (U. S. P.)—Atropine Sulphate
FORMULA: C17H23NO3. MOLECULAR WEIGHT: 288.38.
SYNONYM: Atropia.
"An alkaloid obtained from belladonna. As it occurs in commerce it is always accompanied by a small proportion of hyoscyamine extracted along with it, from which it can not be readily separated"—(U. S. P.).
Preparation.—An easy process for the preparation of Atropine is as follows: One pound of the dry leaves of belladonna are to be boiled in distilled water sufficient to cover them for 2 hours, and the decoction strained off through a coarse cloth into a large precipitating jar. The leaves are again boiled in a second water and the decoctions mixed, to which 2 drachms of strong sulphuric acid are now added; the vegetable albumen is precipitated, and the clear liquor is drawn off with a siphon to a filter. A clear, sherry-colored solution comes through, which is either decomposed by passing gaseous ammonia through it, or by adding commercial carbonate of ammonium. In either case the color becomes changed to black, and crystals of atropine are slowly formed. At the expiration of a day or so the supernatant liquor may be drawn off with a siphon, and the crystals thrown on a filter to dry. To decolorize them, about 1 ounce of spirit of ammonia may be poured on the filter, which washes away most of the coloring matter, leaving the crystals moderately white. Purify by dissolving in boiling alcohol and recrystallizing.
Bouchardat states that by dissolving crude atropine in acidulated water, and then adding an alkaline carbonate to neutralize the acid, a deposit of resinous matter occurs at first, succeeded by a pulverulent precipitate, which is alkaline; this is atropine (though by some has been considered as a distinct substance), and has sometimes received the name of belladonnine.
Description and Tests.—The Pharmacopoeia thus describes atropine: "White, acicular crystals, or a more or less amorphous, white powder, without odor, having a bitter, acrid taste, and gradually assuming a yellowish tint on exposure to air. Soluble at 15° C. (59° F.) in 130 parts of water, 3 parts of alcohol, 16 parts of ether, 4 parts of chloroform, and about 50 parts of glycerin. At about 108° C. (226.4° F.) it melts, forming a colorless liquid; at about 140° C. (284° F.) it begins to give off white, acrid fumes, and, when ignited, it is consumed without leaving a residue. It has a markedly alkaline reaction; its saturated aqueous solution acquires a pink color upon the addition of a drop of phenolphtalein T.S. If a small quantity of atropine, or of one of its salts, be heated with a few cubic centimeters of concentrated sulphuric acid, a peculiar odor recalling that of a mixture of rose, orange-flower, and melilot will become noticeable. On now gradually adding minute fragments of potassium dichromate the odor will change to that of oil of bitter almond, the rose odor disappearing as more dichromate is added. Atropine and its salts are decomposed by prolonged contact with sodium or potassium hydrate, and if heated with either of them evolve ammonia. On dissolving a small quantity (about 0.1 Gm.) of atropine in 2 Cc. of alcohol, and adding an equal volume of mercuric chloride T.S.; a yellow precipitate, which soon turns red, is produced. On adding concentrated sulphuric acid to atropine no color should be produced (absence of readily carbonizable, organic impurities), nor should any color be developed by the subsequent addition of nitric acid (absence of and difference from morphine). The aqueous solution of atropine, or of any of its salts, is not precipitated by platinic chloride T.S. (difference from most other alkaloids). With gold chloride T.S. it gives a precipitate which, when recrystallized from boiling water acidulated with hydrochloric acid, is deposited, on cooling, in minute crystals, forming a yellow, lusterless powder on drying (difference from and absence of more than a small proportion of hyoscyamine)"—(U. S. P.).
The test above referred to, regarding the variety of odors produced as directed, is, beside the physiological (mydriatic) test, probably the most striking and reliable test for this substance. Manganese binoxide and potassium bichromate do not produce, with a sulphuric acid solution of atropine, a blue or purple color, thus showing the difference between this substance and strychnine. Its salts dissolve in water and alcohol, but are not soluble in chloroform and ether.
Chemical Composition.—The principal alkaloids contained in Atropa Belladonna, as atropine, hyoscyarnine, hyoseine, and belladonnine, also atropamine, are substances which bear a close chemical relationship to one another, being partly isomeric and capable of being transformed into one another, e. g., hyoscyamine into atropine (Schuette, 1891; 0. Hesse, 1894).
Atropine and hyoscyamine, both of the formula, C17H23NO3, are capable of being resolved into the alkaloid tropine (C8H15NO) and tropic acid (C9H10O3) by treatment with baryta-water, while hyoscine, under these conditions, is split into pseudotropine (C8H15NO), melting at 106° C. (232.2° F.), and tropic acid.
If in these processes concentrated hydrochloric acid is employed atropic acid (C9H8O2) and its polymer, isatropic acid (C18H16O4) are formed, besides tropic acid. These reactions were first established by Kraut, in 1863, and Lossen, in 1866, find subsequently studied in detail by Ladenburg and other investigators. Tropine was found to be a pyridine derivative, viz.: oxy-ethyl-methyl tetra hydropyridine (C5H7N.[C2H4OH].CH3). It is a strong, tertiary base, forming hygroscopic crystals, which melt at 62° C. (143.6° F.) and boil at 229° C. (445° F.). They are easily soluble in alcohol and water; also soluble in ether. Heated with fuming hydrochloric acid to 180° C. (356° F.) or acted upon by sulphuric acid and glacial acetic acid, the base tropidine, containing 1 molecule less of water, is formed, having the composition C5H6(C2H4)N.CH3, boiling at 162° C. (323.6° F.), and resembling coniine in odor. In 1880 Ladenburg recognized tropic acid to be A-phenyl-B-oxypropionic acid (CH2OH.CHC6H5.COOH). It is soluble in alcohol and ether, to some extent in water, from which solvent it crystallizes in needles or plates, melting at from 117° to 118° C. (242.6° to 246.2° F.). Ɣ Ladenburg, in 1884, succeeded in obtaining atropine by synthesis from its products of decomposition by evaporating a mixture of tropic acid and tropine with hydrochloric acid. By substituting other aromatic acids for tropic acid Ladenburg, in 1884, made known a series of synthetical alkaloids, to which he gave the name tropeïnes, of this series tropine being the common basic constituent. Homatropine (C16H21NO3) he obtained by the action of tropine upon mandelic acid (C6H5.CHOH.COOH) in the presence of hydrochloric acid. (For the chemistry of belladonna alkaloids, also see Belladonna.)
Action and Uses.—(See Atropinae Sulphas.)
