アトロピン 化学特性,用途語,生産方法
性質
C17H23NO3(289.38)．DL-ヒオスシアミンともいう．種々のナス科のAtropa belladonna，Hyoscyamus niger，チョウセンアサガオDatula stramonium，ハシリドコロScopolia japonicaなどの葉および根のなかに含まれるトロパンアルカロイドの一つ．トロピンのD,L-トロパ酸エステル．硫酸塩として精製する．無色の長柱状晶．融点116～118 ℃．エタノール，クロロホルムに易溶，エーテル，熱湯に微溶．副交感神経遮断作用があり，アセチルコリンときっ抗し，どう孔散大，血圧低下，幻覚をもたらす．ヒオスシアミン(融点108 ℃．[α]D"－21°(エタノール))は，トロピンと(－)-トロパ酸のエステルで，共存することが多い．LD50 750 mg/kg(ラット，経口)．森北出版「化学辞典（第2版）
由来
ナス科の植物のベラドンナ，チョウセンアサガオ，ハシリドコロなどの根や茎からとられたアルカロイド。天然にはl‐ヒオスシアミンとして存在するが，抽出によってラセミ(dl‐)体となる。このラセミ体のdl‐ヒオスシアミンをアトロピンという。無色針状結晶で，融点114～116℃。アトロピンの名の由来は，中世のイタリアで婦人が瞳孔散大により美しくなるためベラドンナ(belladonnaは美しい婦人の意)を煎剤として点眼したが，ベラドンナの属名がAtropaであることによる。
医薬用
ナス科の植物に含まれるアルカロイドの一種で、天然にはl‐ヒヨスチアミンとして存在し、抽出の過程でdl体となる。1831年ベラドンナ根より分離された。日本薬局方には硫酸アトロピンとして収載されている。硫酸アトロピンは無臭、無色の結晶または白色結晶性粉末で、水にきわめて溶けやすい。代表的な副交感神経遮断薬（抗コリン薬）で、副交感神経節後線維に働き、アセチルコリンと競合反応をおこして遮断する。また、平滑筋および分泌腺(せん)の機能を抑制することから、消化器や気管支など平滑筋臓器のけいれん緩和に鎮けい剤として、また消化性潰瘍(かいよう)の治療および止汗剤などにも応用される。実際にはアトロピンをおもな有効成分とするロートエキスがよく用いられる。そのほか、瞳孔(どうこう)を広げる作用があるので、眼科では散瞳剤として点眼、注射、内服に用いられる。硫酸アトロピンは毒薬、その製剤は劇薬であり、使用時には十分注意する。副作用として口渇、顔面紅潮、瞳孔散大、乱視、尿閉などがみられる。常用量は1回0.5ミリグラム、1日1.5ミリグラム、極量は1回1ミリグラム、1日3ミリグラム。［幸保文治］
用途
医薬 (マッシュルーム中毒の解毒剤、コリンエステラーゼ阻害剤に対する解毒剤)
効能
散瞳薬, ムスカリン受容体拮抗薬
説明
Atropine is considered to be the
most effective antidote for both OP and CB intoxication.
By effectively competing with acetylcholine for the
same cellular receptors, it prevents overstimulation of
the autonomous parasympathetic system. Most importantly,
it helps prevent asphixia, the main cause of
death. In human subjects, it is customary to constantly
infuse atropine in order to maintain optimal concentration
throughout recovery from the “cholinergic crisis.” In
wildlife rehabilitation, this is impractical and subjects
need to be repeatedly injected with atropine.
化学的特性
Atropine, also known as daturine, C17H23NO3, white, crystalline substance, optically inactive, but usually contains levorotatory hyoscyamine. Compound is soluble in alcohol, ether, chloroform, and glycerol; slightly soluble in water.
物理的性質
Appearance: atropine appears as colourless, odourless crystals or a white crystalline
powder. Solubility: very soluble in water and soluble in ethanol. Melting point:
melting point of atropine isn’t higher than 189?°C (melting time decomposition)
(Chinese Pharmacopoeia), 114–118?°C (United States Pharmacopeia) and 115–
119?°C (British Pharmacopoeia). The chemical structure of atropine is made up of
amino alcohol esters. It is easy for atropine to be hydrolysed into tropine and despun
tropic acid under alkaline condition. Atropine is stable in faintly acid and neutral
aqueous solution, most stable at pH 3.5–4.0.
使用
Atropine is used in medicine and is an antidote for cholinesteraseinhibiting compounds, such as organophosphorus insecticides and certain nerve gases. Atropine is commonly offered as the sulfate. Atropine is used in connection with the treatment of disturbances of cardiac rhythm and conductance, notably in the therapy of sinus bradycardia and sick sinus syndrome. Atropine is also used in some cases of heart block. In particularly high doses, atropine may induce ventricular tachycardia in an ischemic myocardium. Atropine is frequently one of several components in brand name prescription drugs.
定義
An alkaloid that is the 3(s)-endo isomer of atropine.
調製方法
Atropine is prepared by extraction from Datura stramonium, or synthesized. The compound is toxic and allergenic.
適応症
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.
世界保健機関（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.
一般的な説明
Atropine is the tropine ester of racemictropic acid and is optically inactive. It possibly occurs naturallyin various Solanaceae, although some claim, with justification,that whatever atropine is isolated from naturalsources results from racemization of (-)-hyoscyamine duringthe isolation process. Conventional methods of alkaloidisolation are used to obtain a crude mixture of atropine andhyoscyamine from the plant material. This crude mixture isracemized to atropine by refluxing in chloroform or by treatmentwith cold dilute alkali. Because the racemizationprocess makes atropine, an official limit is set on thehyoscyamine content by restricting atropine to a maximumlevorotation under specified conditions.
Atropine occurs in the form of optically inactive, white,odorless crystals possessing a bitter taste. It is not very solublein water (1:460, 1:90 at 80°C) but is more soluble inalcohol (1:2, 1:1.2 at 60°C). It is soluble in glycerin (1:27),in chloroform (1:1), and in ether (1:25). Saturated aqueoussolutions are alkaline in reaction (pH 9.5). The free baseis useful when nonaqueous solutions are to be made, such asin oily vehicles and ointment bases. Atropine has a plasmahalf-life of about 2 to 3 hours. It is metabolized in the liverto several products, including tropic acid and tropine.
危険性
Extremely toxic, poison, paralyzes the
parasympathetic nervous system by blocking the
action of acetylcholine at nerve endings.
健康ハザード
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.
臨床応用
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.
安全性プロファイル
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.
環境運命予測
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.
純化方法
Atropine crystallises from acetone or hot water, and sublimes at ~ 100o/high vacuum. [Beilstein 21/1 V 235.]
アトロピン 上流と下流の製品情報
原材料
準備製品