51-34-3 Usage
Description
Scopolamine is a type of alkaloid that exists in a variety of Solanaceae plants such
as Scopolia japonica, Datura metel L., and so on. It is the main active ingredient in
these plants.Apart from scopolamine, several other chemical ingredients also exist in Scopolia
japonica, including hyoscyamine, anisodamine, anisodine, and so on. Hyoscyamine
is an inhibitor of parasympathetic nerve, with the analgesic and antispasmodic functions, especially for sciatica, sometimes for the treatment of epilepsy, seasickness,
etc., and its pharmacological effects are similar to atropine. However, its clinical
application is less because of its toxicity. The clinical applications of anisodamine
are treating infectious toxic shock, vascular disorders, various neuralgia, smooth
muscle spasms, vertigo, fundus disorders and sudden deafness, and other diseases.
It has definite curative effect and is widely used in clinical in China. Its synthetic
product is called “654-2,” which now still is an effective drug to treat infectious
shock and other vascular diseases. While anisodine is used to treat vascular headache, retinal vasospasm, ischemic optic neuritis, cerebrovascular disease, acute
paralysis, central dysfunction caused by carbon monoxide poisoning, tremor, paralysis, bronchial asthma, motion sickness, organophosphorus pesticide poisoning,
and so on .
Chemical Properties
White or almost white, crystalline powder or colourless crystals.
Physical properties
Appearance: a kind of viscous liquid, brown color. Solubility: soluble in ethanol,
ethyl ether, chloroform, acetone, and water, very soluble in hot water, slightly soluble in benzene and petroleum ether, and also soluble in cold water. It can generate
various crystals with multiple inorganic or organic acids. Melting point: 59±1.0?°C
History
Scopolamine is the main active ingredient of Scopolia japonica, Datura metel L.,
and other Solanaceae plants. As early as 1892, the chemist E.?Schmidt first isolated
it from the Scopolia japonica, so named it as scopolamine. Due to its obvious deficiencies in solubility and usage, the researchers modified its structure as scopolamine butylbromide, which was synthesized and used scopolamine and
bromo-n-butane with heating refluxing method. Preparation method of scopolamine
butylbromide is simple, and it’s easy to be synthesized. There are about 170 domestic enterprises producing its raw materials currently.European Pharmacopoeia (9th ed.), United States Pharmacopeia (36), and the
Japanese Pharmacopoeia (16th ed.) contained bromine scopolamine; British
Pharmacopoeia (2015) contained the raw materials and preparations of scopolamine
butylbromide, including tablets and injections. Pharmacopoeia of the People’s
Republic of China (2015) contained its raw materials, injection, and capsules.
Uses
Different sources of media describe the Uses of 51-34-3 differently. You can refer to the following data:
1. Scopolamine is used for practically the same indications as atropine, but it should be noted
that it has a sedative effect on motor activity, and it is recommended for the treatment of
Parkinsonian symptoms.
2. cholinergic (ophthalmic).
Definition
ChEBI: A tropane alkaloid that is the (S)-tropic acid ester of 6beta,7beta-epoxy-1alphaH,5alphaH-tropan-3alpha-ol.
Brand name
Isopto Hyoscine (Alcon); Transderm-Scop (Ciba-Geigy);Diban;Donnagel-pg;Donnatal;Phenacon;Ru-tuss;Scopoderm tts;Spasmofen;Susano;Tropax.
World Health Organization (WHO)
Scopolamine, an alkaloid with anticholinergic activity extracted
from solanaceous plants, was introduced into medicine in 1888. It is used as a
mydriatic, as an anti-emetic for the control of motion sickness, and for
premedication in general anaesthesia. Shortly after their introduction in the early
1980's, transdermal delivery systems containing scopolamine that were indicated
for the prevention of motion sickness were associated with visual disorders (e.g.
mydriasis, glaucoma) and hallucinations. The action taken in Norway is in
accordance with the legislation in several other countries where these preparations
have always been subjected to prescription control.
General Description
Scopolamine (hyoscine) is found in variousmembers of the Solanaceae (e.g., H. niger, Duboisia myoporoides,Scopolia spp., and Datura metel). Scopolamineusually is isolated from the mother liquor remaining from theisolation of hyoscyamine.Hyoscine is the older name for this alkaloid, althoughscopolamine is the accepted name in the United States.Scopolamine is the levo component of the racemic mixturethat is known as atroscine. The alkaloid is racemized readilyin the presence of dilute alkali.The alkaloid occurs in the form of a levorotatory, viscousliquid that is only slightly soluble in water but very solublein alcohol, chloroform, or ether. It forms crystalline saltswith most acids, with the hydrobromide being the most stableand the most popularly accepted. An aqueous solution ofthe hydrobromide containing 10% mannitol is said to be lessprone to decomposition than unprotected solutions.
Pharmacology
Scopolamine butylbromide, a modified scopolamine, is a peripheral anti-choline
drug; it not only can smooth muscle spasm but also block the ganglion and neuromuscular junction and has the weak effect on center. This drug has stronger effects
on intestinal smooth muscle spasm than atropine and anisodamine; it can selectively
relieve gastrointestinal tract, biliary tract, and urinary tract smooth muscle spasm
and inhibit its peristalsis. Scopolamine butylbromide has less effects on the heart,
pupil, and salivary gland, so it rarely induces central nervous excitement, dilation,
inhibition of saliva secretion, and other adverse reactions, which is unlike atropine.Scopolamine butylbromide is an antagonist of the M cholinergic receptor, its
pharmacological effects are similar to atropine, but it has its own characteristics that
have an obvious advantage in improving blood microcirculation.Oral absorption of scopolamine butylbromide is not easy. It produces efficacy at
2–4?min after intravenous injection, 8–10?min after subcutaneous or intramuscular
injection, and 20–30? min after oral administration, which could maintain about
2–6?h .
Clinical Use
The commercially available transdermal system of scopolaminecomprises an outer layer of polymer film and a drug reservoircontaining scopolamine, polyisobutylene, and mineral oil, which is interfaced with a microporous membrane tocontrol diffusion of the drug. In this dosage form, scopolamineis effective in preventing motion sickness. The actionis believed to be on the cortex or the vestibular apparatus.Whereas atropine stimulates the CNS, causing restlessnessand talkativeness, scopolamine usually acts as a CNSdepressant.
Safety Profile
Poison by intravenous, intraperitoneal, and subcutaneous routes. Moderately toxic by ingestion. Human systemic effects from very small amounts by subcutaneous and intramuscular routes: changes in surface EEG, dstorted perceptions, excitement, hallucinations, and mydriasis. It can cause the individual who is affected to lose a certain amount of his normal inhibitory control. It is for that reason that it has been called “truth serum.” An experimental teratogen. Experimental reproductive effects. Human mutation data reported. In many cases of poisoning from ths material, and even to a certain extent following its medcal application, there is retention of the urine caused by paralysis of the bladder, and catheterization is necessary. The fatal dose is variable. Death has occurred from as little as 0.6 mg, whde recovery has occurred from doses of 7-1 5 mg. An anticholinergc drug. When heated to decomposition it emits highly toxic fumes of NOx. See also ESTERS
Synthesis
Scopolamine, the L-9-methyl-3-oxa-9-azatricyclo[3.2.1.0.2,4]non-7-yl ester
of α-hydroxymethylphenylacetic acid (14.1.6), can be synthesized from tropenol (14.1.2)
by oxidizing the double bond between carbon atoms C6 and C7 of the tropine ring, giving an epoxide derivative, scopine (14.1.5). Esterification of this product using tropic acid
gives scopolamine (14.1.6) [7,8].
Metabolism
It is almost completely metabolized in the liver and is excreted via the kidneys. Its elimination
half-life is approximately 8 hours.
Purification Methods
Crystallise it from *benzene/pet ether, EtOH or H2O. It is polymorphic with m 165-166o and 190-191o. The racemate has m 56-57o (H2O), 37-38o (2H2O), syrup (anhydrous), l and d isomers can separate as syrups when anhydrous. [Beilstein 27 H 99, 102, 27 I 247-248, 27 II 43-44, 27 III/IV 1790.]
Check Digit Verification of cas no
The CAS Registry Mumber 51-34-3 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 1 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 51-34:
(4*5)+(3*1)+(2*3)+(1*4)=33
33 % 10 = 3
So 51-34-3 is a valid CAS Registry Number.
InChI:InChI=1/C9H10O3.C8H13NO2/c10-6-8(9(11)12)7-4-2-1-3-5-7;1-9-5-2-4(10)3-6(9)8-7(5)11-8/h1-5,8,10H,6H2,(H,11,12);4-8,10H,2-3H2,1H3
51-34-3Relevant articles and documents
The Assignment of the Absolute Configuration of β-Chiral Primary Alcohols with Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid
Kriegelstein, Michal,Profous, David,P?ibylka, Adam,Canka?, Petr
, p. 12912 - 12921 (2020/11/23)
Axially chiral trifluoromethylbenzimidazolylbenzoic acid (TBBA) was used as a chiral derivatization agent for the assignment of the absolute configuration of β-chiral primary alcohols. The structures varied from simple aliphatic alcohols to complex cyclic systems and highly substituted sugar derivatives. The NMR-based method was successfully implemented to evaluate 17 compounds and displayed ΔδPM values higher than 0.1 ppm in most cases, which makes TBBA superior to MTPA and MPA and comparable to 9-AMA.
Buscopan labeled with carbon-14 and deuterium
Latli, Bachir,Stiasni, Michael,Hrapchak, Matt,Li, Zhibin,Grinberg, Nelu,Lee, Heewon,Busacca, Carl A.,Senanayake, Chris H.
, p. 557 - 564 (2016/11/23)
Hyosine butyl bromide, the active ingredient in Buscopan, is an anticholinergic and antimuscarinic drug used to treat pain and discomfort caused by abdominal cramps. A straightforward synthesis of carbon-14– and deuterium-labeled Buscopan was developed using scopolamine, n-butyl-1-14C bromide, and n-butyl-2H9 bromide, respectively. In a second carbon-14 synthesis, the radioactive carbon was incorporated in the tropic acid moiety to follow its metabolism. Herein, we describe the detailed preparations of carbon-14– and deuterium-labeled Buscopan.
Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna
Li, Jing,Van Belkum, Marco J.,Vederas, John C.
experimental part, p. 4356 - 4363 (2012/08/28)
(-)-Hyoscyamine, the enantiomerically pure form of atropine, and its derivative scopolamine are tropane alkaloids that are extensively used in medicine. Hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a monomeric α-ketoglutarate dependent dioxygenase, converts (-)-hyoscyamine to its 6,7-epoxy derivative, scopolamine, in two sequential steps. In this study, H6H of Atropa belladonna (AbH6H) was cloned, heterologously expressed in Escherichia coli, purified and characterized. The catalytic efficiency of AbH6H, especially for the second oxidation, was found to be low, and this may be one of the reasons why Atropa belladonna produces less scopolamine than other species in the same family. 6,7-Dehydrohyoscyamine, a potential precursor for the last step of epoxidation, was shown not to be an obligatory intermediate in the biosynthesis of scopolamine using purified AbH6H with an in vitro 18O labeling experiment. Moreover, the nitrogen atom in the tropane ring of (-)-hyoscyamine was found to play an important role in substrate recognition.
