51-55-8 Usage
Uses
Used in Medicine:
Atropine is used as an anticholinergic agent for its various effects on the body, such as dilating the pupils, increasing heart rate, reducing salivation and other secretions, and as an antidote for cholinesterase-inhibiting compounds, such as organophosphorus insecticides and certain nerve gases.
Used in Veterinary Medicine:
Atropine is used as a preanesthetic agent and in the treatment of motion sickness in animals.
Used in Ophthalmology:
Atropine is used as a mydriatic agent to dilate the pupils for eye examinations and surgeries.
Used in Cardiology:
Atropine is used in the treatment of disturbances of cardiac rhythm and conductance, notably in the therapy of sinus bradycardia and sick sinus syndrome, and in some cases of heart block.
Used in Antidote Therapy:
Atropine is considered the most effective antidote for organophosphate and carbamate intoxication, preventing overstimulation of the autonomous parasympathetic system and helping to prevent asphyxia.
Physical Properties:
Atropine appears as colorless, odorless crystals or a white crystalline powder. It is very soluble in water and soluble in ethanol. The melting point of atropine isn't higher than 189°C (melting time decomposition) according to the Chinese Pharmacopoeia, 114–118°C according to the United States Pharmacopeia, and 115–119°C according to the British Pharmacopoeia. Atropine is stable in faintly acid and neutral aqueous solutions, most stable at pH 3.5–4.0.
Chemical Properties:
Atropine, also known as daturine, C17H23NO3, is a white, crystalline substance that is optically inactive but usually contains levorotatory hyoscyamine. It is soluble in alcohol, ether, chloroform, and glycerol; slightly soluble in water. Atropine has a plasma half-life of about 2 to 3 hours and is metabolized in the liver to several products, including tropic acid and tropine.
Pharmacokinetics
It can be quickly absorbed by the gastrointestinal tract after oral administration and quickly distributed to the body tissue. It can also penetrate through the placenta into the fetal circulation. Clinical studies have shown that after intramuscular injection of 2 mg, 85 ~ 88% is subject to urine excretion within 24 hours. Approximately 5% of them were found in their prototypes and 33% of their metabolites; only a small amount was excreted in feces and other secretions.
Side effects
Dry mouth, blurred vision, heart palpitations, dry skin and constipation. High-dose poisoning switches excitement into inhibition, causing coma and respiratory paralysis and death.
Production
It can be extracted from the root of Solanaceae Scoparia Anisodus tanguticus or Himalayan Scoparia; can also be obtained by artificial synthesis.
Belladonna leaf is extracted out of the scopolamine (L-body), followed by racemization, recrystallization to make it.
Toxicity grade
highly toxic
Acute Toxicity
Oral - Rat LD50: 500 mg / kg; Oral - Mouse LD50: 75 mg / kg
Flammability Hazard characteristics
Flammable; Combustion produces toxic nitrogen oxide fumes; Patient medication side effects: Visual changes; Dilated pupils, Muscle weakness.
Storage and transportation
Ventilated, dry and low temperature; Separated from foodstuffs in storehouse
Originator
Atromed,Promed Exports,India
History
Mandragora (mandrake) was described for treatment of wounds, gout and sleeplessness and as a love potion in the fourth century BC by Theophrastus. Atropine
extracted from the Egyptian henbane was used by Cleopatra in the last century BC
to dilate her pupils in the hope that she would appear more alluring. In the
Renaissance, women used the juice of the berries of Atropa belladonna to enlarge
the pupils of their eyes for cosmetic reasons.
It isn’t until the first century AD that Dioscorides found that wine containing
mandrake can be used as an anaesthetic treatment for pain or sleeplessness in surgery or cautery. The combination of extracts containing tropane alkaloids and opium
was used to treat diseases, which was popular in the Roman and Islamic Empires
and Europe. The combination was replaced by the use of ether, chloroform and
other modern anaesthetics about 100?years ago.
The mydriatic effects of atropine were studied by the German chemist Friedlieb
Ferdinand Runge (1795–1867). In 1831, the German pharmacist Heinrich F.? G.
Mein (1799–1864) succeeded in separating pure atropine from plants. The substance was first synthesized by German chemist Richard Willst?tter in 1901.
In 1889, Richard Willst?tter first confirmed the chemical structure of atropine.
Atropine was first synthesized by A.?Ladenburg. Homatropine, a kind of tropic alkaline ester, is used in the diagnosis and treatment in ophthalmology, and it has a
shorter acting time than atropine. Quaternary ammonium compounds of atropine
obtained by alkylation of nitrogen atoms have anticonvulsant function, which does
not affect the central nervous system, due to their polarity. In 1970, atropine sulphate was synthesized in Hangzhou, the location of the first pharmaceutical factory
in China, which increased the yield, reduced the cost and met the requirements of
clinics.
Production Methods
Atropine is prepared by extraction from Datura stramonium, or synthesized. The compound is toxic and allergenic.
Indications
This product was recorded in the Pharmacopoeia of the People’s Republic of China
(2015), the British Pharmacopoeia (2017), the United States Pharmacopeia (40), the
Japanese Pharmacopoeia (17th ed.), the Indian Pharmacopoeia (2010), the European
Pharmacopoeia (9.0th ed.), the International Pharmacopoeia (5th ed.) and the
Korean Pharmacopoeia (10th ed.).
Atropine sulphate is commonly used in clinics. Dosage forms are injection, tablet and eye ointment; atropine sulphate was mainly used to treat toxic shock and
organic phosphorus pesticide poisoning, to relieve visceral colic, as preanaesthetic
medication and to reduce bronchial mucus secretion. The indications of atropine
sulphate eye gel are iridocyclitis, fundus examination and mydriasis.
Manufacturing Process
Atropin was obtained from belladonna roots and by racemisation of Lhyoscyamine
with dilute alkali or by heating in chloroform solution. The
alkaloid was crystallised from alcohol on addition of water, or from chloroform
on addition of light petroleum, or from acetone in long prisms, m.p. 118°C,
sublimed unchanged when heated rapidly. It is soluble in alcohol or
chloroform, less soluble in ether or hot water, sparingly so in cold water (in
450 L at 25°C) and almost insoluble in light petroleum. Atropine is optically
inactive.
Therapeutic Function
Anticholinergic
World Health Organization (WHO)
Atropine, an alkaloid with anticholinergic activity extracted from
Atropa belladonna, has been widely used in medicines for centuries for its
antispasmodic and mydriatic properties. It is also used for premedication prior to
anaesthesia. Preparations containing atropine remain available and the substance
is included in the WHO Model List of Essential Drugs.
Hazard
Extremely toxic, poison, paralyzes the
parasympathetic nervous system by blocking the
action of acetylcholine at nerve endings.
Health Hazard
The toxic effects are similar to atropine. Thesymptoms at toxic doses are dilation of the pupils, palpitation, blurred vision, irritation,confusion, distorted perceptions, hallucinations,and delirium. However, the mydriaticeffect is stronger than that of many othertropane alkaloids. Scopolamine is about threeand five times more active than hyocyamineand atropine, respectively, in causing dilationof the pupils. Its stimulating effect on thecentral nervous system, however, is weakerthan that of cocaine but greater than thatof atropine. The oral LD50 value in mice iswithin the range of 1200 mg/kg.The histidine reversion–Ames test formutagenicity gave inconclusive results.
Pharmacology
Atropine is a blocker of typical M-choline receptor. In addition to terminating the
gastrointestinal smooth muscle spasm, inhibiting glands, dilating pupils, increasing
intraocular tension, adjusting vision through paralysis, accelerating heart rate and
dilating bronchi, large doses of atropine dilate blood vessels, terminating the spasmodic contraction and improving minicirculation. Atropine can excite or inhibit the
central nervous system in a dose-dependent manner. Atropine exerts longer and
stronger effect on heart, intestine and bronchial smooth muscle than other belladonna alkaloids. Atropine also relaxes the pupillary sphincter and the ciliary muscle
and dilates the pupils by blocking M-choline receptor in ocular tissue.
Blockers of M-choline receptor included atropine, scopolamine, anisodamine
and anisodine. Belladonnas not only block M-choline receptor in internal organ
cells but also in the central nervous system. Compared with atropine, scopolamine
has an oxygen bridge, which increases central nervous system function. The oxygen
bridge of scopolamine is partially broken and then becomes anisodamine, which
is difficult to pass through the blood-brain barrier, and symptoms caused by atropine
in the central nervous system were less than that caused by atropine.
Peak concentration of plasma can be reached at 15–20?min after intramuscular
injection of atropine and at 1–2?h after oral administration and can last for 4–6?h.
Most of the atropine can be absorbed by the gastrointestinal tract and other mucous
membranes, and a little of the atropine can be absorbed by the eyes and skin. The t1/2
is 3.7–4.3?h. Binding rate of plasma protein is 14–22%. Volume of distribution is
1.7?L/kg after oral administration. Atropine can rapidly distribute to different organ
systems and pass the blood-brain barrier and the placenta.
After absorption by the eye’s conjunctiva, 30% of the products are excreted
unchanged via the kidneys; the others become metabolites by hydrolysis and glucuronidation or glucosidation. After 1% gel eye drop, enlarged pupil function lasts
for 7–10?days, and regulatory paralysis lasts for 7–12?days.
Clinical Use
The best known of the muscarinic blocking drugs are the
belladonna alkaloids, atropine (Atropine) and scopolamine
(Scopolamine).They are tertiary amines that contain
an ester linkage. Atropine is a racemic mixture of
DL-hyoscyamine, of which only the levorotatory isomer is
pharmacologically active.Atropine and scopolamine are
parent compounds for several semisynthetic derivatives,
and some synthetic compounds with little structural similarity
to the belladonna alkaloids are also in use.All of
the antimuscarinic compounds are amino alcohol esters
with a tertiary amine or quaternary ammonium group.
Safety Profile
Poison by ingestion,
subcutaneous, intravenous, and
intraperitoneal routes. Human systemic
effects by ingestion and intramuscular
routes: visual field changes, mydriasis
@updlary dtlation), and muscle weakness.
An experimental teratogen. Other
experimental reproductive effects. An
alkaloid. When heated to decomposition it
emits toxic fumes of NOx.
Synthesis
Atropine, the D,L-8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester of α-hydroxymethyl
phenylacetic acid (14.1.4), can be synthesized by a standard scheme of synthesizing of
tropane alkaloids. Condensation of maleyl aldehyde with methylamine and acetonedicarboxylic acid gives tropenone (14.1.1), which is the main starting material for the synthesis of
both atropine and scopolamine. The carbonyl group of tropenone is reduced, thus forming
tropenol (14.1.2), after which the double bond between C6 and C7 of the tropane ring is
hydrogenated, giving tropine (14.1.3). Esterification of the tropenol gives the desired
atropine (14.1.4) [1–6].
Environmental Fate
Atropine competitively antagonizes acetylcholine at the neuroreceptor
site. Atropine prevents acetylcholine from exhibiting
its usual action but does not decrease acetylcholine production.
Cardiac muscle, smooth muscle, and the central nervous
system are most affected by the antagonism of acetylcholine.
Purification Methods
Atropine crystallises from acetone or hot water, and sublimes at ~ 100o/high vacuum. [Beilstein 21/1 V 235.]
Toxicity evaluation
Free atropine is only slightly soluble in cold water. It melts at
115°C but decomposes upon boiling.Environmental monitoring of atropine is not routinely
performed by regulatory bodies. Hazardous short-term degradation
products are not likely to occur. Accidental environmental
exposure may occur through unintentional ingestion of
toxic plants of the Solanaceae family, such as the deadly
nightshade.
Check Digit Verification of cas no
The CAS Registry Mumber 51-55-8 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, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 51-55:
(4*5)+(3*1)+(2*5)+(1*5)=38
38 % 10 = 8
So 51-55-8 is a valid CAS Registry Number.
InChI:InChI=1/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13-,14+,15+,16?
51-55-8Relevant articles and documents
Kinetic and polarographic study on atropine N-oxide: its obtaining and polarographic reduction
Dubenska, Liliya,Dushna, Olha,Blazheyevskiy, Mykola,Pysarevska, Solomiya,Klymiuk, Iryna
, p. 4147 - 4155 (2021)
The work presents the obtaining of atropine N-oxide using various peroxyacids (organic monoperoxyacid, diperoxyacids and inorganic peroxyacids). The kinetics of atropine oxidation with various oxidants, for example Oxone, m-chloroperoxybenzoic acid, diperoxysebasic acid and diperoxyazelaic acid, was studied. The optimal conditions for obtaining of atropine N-oxide (oxidation duration, pH) are given in the work. It was established that the best oxidant was potassium peroxymonosulfate, since 100% yield of atropine N-oxide was achieved within 15?min. In this work, we showed that the oxidation reaction of atropine to N-oxide was a second-order reaction. The rate constants of these reactions were established. The electrochemical behavior of atropine N-oxide obtained using potassium peroxymonosulfate and m-chloroperoxybenzoic acid on a mercury dropping electrode was investigated. Atropine N-oxide was reduced forming two peaks. Each reduction peak involved 1 electron and 1 proton.
Synthesis method of atropine sulfate
-
, (2021/09/01)
The invention belongs to the field of chemical synthesis, and particularly relates to a preparation method of atropine sulfate. The preparation method comprises the following steps: firstly preparing tropine ester, then preparing atropine, salifying to prepare atropine sulfate, and finally refining to obtain the product. In the preparation process of the tropine ester, the reaction temperature is strictly controlled to be 105-111 DEG C, and the crystallization temperature is controlled to be 0-5 DEG C, so that the yield of the tropine ester is improved. In the process of preparing atropine through reduction reaction, palladium-carbon is adopted as a catalyst, and the reaction temperature is strictly controlled to be 10-15 DEG C, so that the product quality is effectively improved. Sulfuric acid is diluted by preparing a sulfuric acid ethanol solution, and the dripping speed of the sulfuric acid ethanol solution is controlled, so that the stable quality of atropine sulfate is ensured.
Synthesis method of atropine and atropine sulfate
-
, (2020/07/02)
The invention provides a synthesis method of atropine and atropine sulfate, which comprises the following steps: carrying out acetylation reaction on tropine acid to form acetyl tropine acid, reactingthe acetyl tropine acid with a chlorination reagent to form acyl chloride, reacting the acyl chloride with tropine alcohol, removing acetyl to obtain atropine, and salifying atropine and sulfuric acid to obtain atropine sulfate. The whole synthesis process can be completed by adopting a one-pot reaction, additional steps for completing the process by isolating intermediates are avoided, the reaction conditions are mild, the steps are simple, the yield is high, the purity is high, and the method is suitable for large-scale industrial production.
Method for preparing atropine
-
Paragraph 0065-0083, (2019/11/19)
The present invention relates to a method for manufacturing atropine. More specifically, the present invention relates to the method for manufacturing atropine which can manufacture and crystallize atropine by effectively removing impurities remaining in a crude atropine sulfate monohydrate using activated carbon and leaving sulfate by an acid-base reaction, thereby being able to obtain high purity atropine.(AA) 5802/atropine(BB) AtropineCOPYRIGHT KIPO 2020
Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine
Bédard, Anne-Catherine,Longstreet, Ashley R.,Britton, Joshua,Wang, Yuran,Moriguchi, Hideki,Hicklin, Robert W.,Green, William H.,Jamison, Timothy F.
supporting information, p. 6233 - 6241 (2017/09/30)
Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9.
An anti-choline medicine preparation method of atropine sulfate
-
, (2017/03/08)
The invention provides a synchronizing method of atropine sulphate. The method is characterized in that hydrolyzing methyl phenoxyacetate (II) is hydrolyzed to obtain a compound (III); the compound (III) and thionyl chloride are subjected to acylation reaction to obtain a compound (IV); the compound (IV) and 8-methyl-8-azabicyclo[3.2.1]oct-3-alchol are subjected to condensation reaction to obtain a compound (V); the compound (V) and paraformaldehyde are used for producing atropine (VI) under an alkaline condition; the atropine (VI) is salified under an acidic condition to obtain the atropine sulphate (I). The preparation method is simple in technology, high in yield, high in purity, low in monomer impurity and easy for industrial production.
Can Accelerated Reactions in Droplets Guide Chemistry at Scale?
Wleklinski, Michael,Falcone, Caitlin E.,Loren, Bradley P.,Jaman, Zinia,Iyer, Kiran,Ewan, H. Samuel,Hyun, Seok-Hee,Thompson, David H.,Cooks, R. Graham
, p. 5480 - 5484 (2016/11/26)
Mass spectrometry (MS) is used to monitor chemical reactions in droplets. In almost all cases, such reactions are accelerated relative to the corresponding reactions in bulk, even after correction for concentration effects, and they serve to predict the likely success of scaled-up reactions performed in microfluidic systems. The particular chemical targets used in these test studies are diazepam, atropine and diphenhydramine. In addition to a yes/no prediction of whether scaled-up reaction is possible, in some cases valuable information was obtained that helped in optimization of reaction conditions, minimization of by-products, and choice of catalyst. In a variant on the spray-based charged droplet experiment, the Leidenfrost effect was used to generate larger, uncharged droplets and the same reactions were studied in this medium. These reactions were also accelerated but to smaller extents than in microdroplets, and they gave results that correspond even more closely to microfluidics data. The fact that MS was also used for online reaction monitoring in the microfluidic systems further enhances the potential role of MS in exploratory organic synthesis.
PROCESS FOR PREPARATION OF ATROPINE
-
, (2016/03/12)
A process for the production of atropine is provided. The process provides for a new, efficient and commercially feasible synthetic process for the preparation of atropine and atropine salts. In one aspect, a one pot process for the synthesis of atropine is provided. The process provides excellent yield and can be used to prepare commercial 5 scale batches of atropine or atropine salts. The process avoids the additional steps of having to isolate intermediates to complete the process and has the advantage of proceeding efficiently at ambient temperature for many of the steps. The process includes providing acetyltropoyl chloride and reacting the acetyltropoyl chloride with tropine followed by a contact with an acid to form atropine.
CRYSTALLINE ATROPINE SULFATE
-
, (2014/07/21)
The present invention relates to crystalline polymorph form of Atropine sulfate and process for the preparation thereof.
N-Demethylation of N-methyl alkaloids with ferrocene
Kok, Gaik B.,Scammells, Peter J.
supporting information; experimental part, p. 4499 - 4502 (2010/09/15)
Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach.
