Scopolamines

Synonyms /-scopolamine 6,7-epoxytropine tropate scopine tropate hyoscine 6-j6- 

Scopolamine is found in the leaves of Datura metel L., D. meteloides L., and D. fastuosa var. alba (Cordell 1978). It is used as a sedative, a preanesthetic agent, and in the treatment of motion sickness (Merck 1989). 

Colorless viscons liquid decomposes on standing forms a crystalline monohydrate moderately solnble in water (10 g/100 g at 20°C 68°F), dissolves readily in hot water, alcohol, ether, acetone, and methylene chloride slightly solnble in petroleum ether, benzene, and tolnene. It is readily hydrolyzed when mixed with acids and alkalies. 

The toxic effects are similar to atropine. The symptoms at toxic doses are dilation of the 

The histidine reversion-Ames test for mutagenicity gave inconclusive results. 

In lower mammals, scopolamine reduces the excitability of the motor areas as tested by electric shocks, and the reflex excitability in the frog is not increased as by atropine. Scopolamine appears to be excreted or destroyed in the tissues much more rapidly than atropine, for its effects last a shorter time. 

The action of scopolamine, then, seems to correspond with that of atropine, except that the central nervous system is here depressed, while the action on the peripheral structures is of shorter duration. It depresses the brain in very small quantities 0.5 mg is generally sufficient to induce 

Scopolamine is much less reliable as a hypnotic than morphine or the members of the chloral hydrate group. It is most effective when sleep is prevented by motor excitement, and the sleep seems to arise from the relief of this condition and not from depression of the consciousness. 

Scopolamine is levorotary to polarized light the racemic form, atroscine, which is often present in commercial scopolamine, acts only half as strongly on the peripheral organs, because in it the levorotary is mixed with the dextrorotary isomer, which is almost inactive. The cerebral action is equal, however, in the two forms. 

THREE-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

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The physiologically and commercially important alkaloids of this group of compounds, occurring widely ia the Solanaceae and Convolvoulaceae as weU as the Erythroxylaceae, iaclude not only cocaine (11) but also atropiae (41) and scopolamine (42). 

Scopolamine (42), an optically active, viscous Hquid, also isolated from Solanaceae, eg. Datura metell. decomposes on standing and is thus usually both used and stored as its hydrobromide salt. The salt is employed as a sedative or, less commonly, as a prophylactic for motion sickness. It also has some history of use ia conjunction with narcotics as it appears to enhance their analgesic effects. BiogeneticaHy, scopolamine is clearly an oxidation product of atropiae, or, more precisely, because it is optically active, of (—)-hyoscyamiae. 

Despite the limitations imposed by the physiology of the skin, several marketed controUed release transdermal dmg dehvery systems are available in the United States for example, scopolamine [51-34-3] for the treatment of motion sickness, nitroglycerin [55-63-0] for angina, estradiol [50-28-2] for the rehef of postmenopausal symptoms and osteoporosis, clonidine [4205-90-7] for the treatment of hypertension, fentanyl [437-38-7] as an analgesic, and nicotine [54-11-5] as an aid to smoking cessation. These systems are designed to dehver dmg for periods of one to seven days. 

Panase 21/100 e/scopolamine/phenobarbital pancreatic enzymes QuaHtest... 

Scopolamine Antispasmodic Low/bigb Datw asti amonium... 

However, these absorption spectra can be employed as an aid to charaeterization, particularly when authentic reference substanees are ehromatographed on a neighboring track. The use of differential speetrometry yields additional information [64]. Quantitative analysis is usually performed by scanning at the wavelength of greatest absorbance (2m ). However, determinations at other wavelengths can sometimes be advantageous, e.g. when the result is a better baseline. An example is the determination of scopolamine at 2 = 220 nm instead of at =... 

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. 

M. and M. Polonovski found that when scopolamine is treated with hydrogen peroxide, there is formed in addition to scopolamine iV-oxide [a]i, — 14° (H2O), [B. HBr, m.p. 153°] the quaternary base scopinium, isolated in the form of its bromide, m.p. 209-10°. The latter is reduced by sodium amalgam to a tertiary base, stereoisomeric with scopine and related to the latter as -tropine is to tropine and, therefore, named -SCOPINE. It yields crystalline salts B. HCl, m.p. 257-8°, aurichloride. 

Sauroxine saururine, 753, 7S4 Saussufea Cappa saussurine, 782 Sceleranecic acid, 605 Sceleratlne, 602, 605 Schcenocaulon officinale, 700 Scopine, 64, 66, 88, 107 -scopine, 89 ncr-0-scopine, 89 Scopolamine, see Hyoscine ... 

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

In a one-liter separatory funnel, 94 g (0.215 mol) of scopolamine hydrobromide trihydrate was dissolved in 250 ml of water, made alkaline by shaking with 40 g (1 mol) of sodium hydroxide in 150 ml of water, and the free base immediately extracted with ether. As scopolamine is somewhat soluble in water, the aqueous layer was saturated with potassium carbonate and again extracted with ether. The combined ether extracts were dried over anhydrous magnesium sulfate and the ether removed by distillation, leaving 65 g (0.214 mol 100% yield) of nearly colorless oil. Then 100 g (1.05 mols) of cold methyl bromide was added to a chilled, 500-ml pressure flask containing the 65 g of scopolamine, the flask stoppered tightly with a clamp, and allowed to stand at room temperature for 96 hours. 

The flask was cooled before opening, excess methyl bromide removed by filtration, and the white solid washed thoroughly with dry ether. The yield of crude scopolamine methyl bromide was 80 g (94% yield 93.5% over-all yield). 

The salt was recrystallized from 550 ml of alcohol first crop, 70 g, MP 212° to 214°C second crop, 6 g, MP 195° to 200°C. The combined crops were again recrystallized from 500 ml of 3-A alcohol MP 210° to 212°C. The third recrystallization from 600 ml of alcohol yielded 64 g, MP 214° to 216°C, a 75% yield based on scopolamine hydrobromide trihydrate starting material. 

An example of the procedure is shown in Figure 6.22. Specifically, a series of Schild analyses were done for the reference antagonist scopolamine in the presence of different concentrations of the test antagonist atropine. The resultant plot according to Equation 6.38 yields an estimate of the KB for atropine as the intercept (Log (k— 1) = 0). If atropine had secondary effects on the system, this procedure will cancel them and allow measurement of the receptor antagonism. An example of this procedure is given in Section 12.2.5. 

Dose-response curves to the agonist carbachol are obtained in the presence and absence of the antagonist scopolamine. The data are given in Table 12.6a. Responses are contractions of rat trachea resulting from muscarinic receptor... 

Test antagonist = atropine. Reference antagonist = scopolamine. The Schild regression is obtained to the concentrations of scopolamine shown in the left-hand column in the presence of the concentrations of atropine shown in columns labeled Regression I to IV. ... 

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