Scopolamine Hyoscine

Transdermal scopolamine (hyoscine) was introduced in the 1980s as a convenient alternative for the prevention of motion sickness. It is also effective in reducing of nausea and vomiting after ear surgery but was not found to be useful in the prevention of vasovagal syncope (see Chapter 14). 

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These include atropine, scopolamine (hyoscine), trihexyphenidyl (benzhexol) and benzatropine. They block central muscarinic receptors involved in various afferent pathways of the vomiting reflex (Fig. 1). They have been used to control motion sickness, emesis in Meniere s disease and postoperative vomiting. Currently, hyoscine is largely restricted to the treatment of motion sickness where it has a fast onset of action but a short duration (4-6 h). Administration of hyoscine by transdermal patch produces a prolonged, low-level release of the drug with minimal side effects. To control postoperative vomiting, it should be applied >8 h before emesis is anticipated. 

Atropine and its ether analog scopolamine (hyoscine) are potent alkaloids that are found as active compounds in a large number of plants around the world (belladonna alkaloids). The deadly nightshades ( European bittersweet, Solanum dulcamara or belladonna, belladonna) were used in the Mid-... 

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. ... 

Tropane alkaloids Tropane Atropine Cocaine Hyoscyamine Scopolamine/ hyoscine... 

Atropine and its naturally occurring congeners are tertiary amine alkaloid esters of tropic acid (Figure 8-1). Atropine (hyoscyamine) is found in the plant Atropa belladonna, or deadly nightshade, and in Datura stramonium, also known as jimsonweed (Jamestown weed), sacred Datura, or thorn apple. Scopolamine (hyoscine) occurs in Hyoscyamus niger, or henbane, as the /(-) stereoisomer. Naturally occurring atropine is /(-)-hyoscyamine, but the compound readily racemizes, so the commercial material is racemic d,/-hyoscyamine. The /(-) isomers of both alkaloids are at least 100 times more potent than the d(+) isomers. 

Scopolamine (hyoscine N-butylbromide) is available as an antispasmodic product (20 mg ampule for injection and 20 mg tablets) for use in humans. In addition, there is a veterinary product that contains scopolamine and dipyrone approved for use as an antispasmodic/analgesic in animals. In addition to blocking the effects of acetylcholine at the muscarinic receptor, scopolamine affects nicotinic receptors in intestinal ganglia and does not affect the CNS. In horses, scopolamine is used as an antispasmodic and to relax the rectum to facilitate abdominal palpation. In one report, 0.2 mg/kg was as effective as 0.2 mg/kg scopolamine plus 2.5 mg/kg dipyrone in relieving discomfort caused by balloon dilatation of the cecum (Roelvink et al 1991). The analgesic effect tasted for 20 min. 

Scopolamine. Scopolamine (hyoscine) is found in various members of the Solanaceae (e.g.. H. niger. Duhoisiu myt>i>ornidt x. Scolwlia. spp.. and Diilura metel). Scopolamine usually is isolated from the mother liquor remaining from the isolation of hyoscyamine. 

The carbon a to the carboxyl group of tropic add is asymmetric and is easily racemized during the isolation of the solanaceous alkaloids. Atropine and atroscine are racemic forms. The corresponding levo isomers, (-)-hyoscyamine and (-)-scopolamine(hyoscine), occur naturally in the solanaceous plants. 

Scopola. Dried rhizome of Scopola cantiolica Jacq., Satanaceae. Habit. Germany (Bavaria), Hungary, Russia. Constit. Scopolamine (hyoscine). atropine, hyoscy-amine total about 0.7% alkaloids. 

From a pharmaceutical point of view, three natural-occurring compounds are widely used as chemotherapeutic agents viz. (-)-hyoscyamine, (-)-scopolamine (hyoscine) and atropine (Fig. 2). The latter compound is formed by the racemization of (-)-hyoscyamine during isolation and purification and is thus ( )-hyoscyamine. All three compounds are esters of 3a-tropine with tropic acid. 

The most commonly used muscarinic receptor antagonist is scopolamine (hyoscine), which usually is administered as the free base in the form of a transdermal patch (transdee(M-scop). Its principal utility is in the prevention and treatment of motion sickness, although it also has some activity in postoperative nausea and vomiting. In general, anticholinergic agents have no role in chemotherapy-induced nausea. 

SCOPOLAMINE [Merck Index ii 8361 12 8550] [7 ) (iot.2-P.4P>5tt,7p)]-a-(hydrox7raethyI)benzeneacetic acid 9-methyl-3-oxa-9-azatricyclo-[3.3.i.o ]non 7 yl ester hyoscine Scopo-derm TTS Transderm-V Scopolamin Hyoscin hyoscine... 

The term anticholinergic as used in the context of this discussion refers more specifically to compounds that selectively block the brain s muscarinic receptor (now known to consist of several sub-types). Atropine (hyoscyamine) and scopolamine (hyoscine) are the most familiar medicinal anticholinergics. Historically, they were obtained from of the botanical family Solanaceae, which includes Jimson (or loco) weed, mandrake root, henbane, belladonna, and nightshade. Atropine and scopolamine are esters of tropic acid and contain a tertiary nitrogen moiety. This gives them the ability to cross the blood-brain barrier and block central muscarinic cholinergic receptors by competitive inhibition with acetylcholine, the natural neurotransmitter at these sites. 

PoETHKE et al. [125, 173] have worked with belladonna herbs and tinctures. They used silica gel G and chloroform-acetone-diethylamine (50 + 40 + 10) as solvent. Oswald and Flhck [151—153] have chromatographed hyoscyamine and other alkaloids from this material, notably belladonnine, apoatropine, aposcopolamine, scopine and scopoline. Six solvents were used, of which the best was found to be butanone-methanol-7.5% ammonium hydroxide (60 + 30 + 10) the Dragendorff reagent was employed for detection. The method was worked out also for quantitative determination (planimetric evaluation) (limit of error 5.8%). A linear relation was found between spot area and amount of alkaloid, provided that the amount of substance did not fluctuate by more than 20%. In this way it was possible to determine the mixture of hyoscyamine and atropine in the presence of scopolamine (hyoscine) in some of the plant organs of Atropa belladonna. Datura stramonium, Hyoscyamus niger and H. muticus [153]. 

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