ピロカルピン 化学特性,用途語,生産方法
性質
C11H16N2O2(208.26)．ピロカルピンは，南アメリカ産ミカン科ヤボランジ(主としてPilocarpus microphyllus)の葉に含まれる主アルカロイド．イミダゾール骨格をもつ数少ないものの一つ．白色の針状晶．融点34 ℃，沸点260 ℃(666 Pa)．[α]D"＋106°(水)．瞳孔縮小作用がある．塩酸塩(塩酸ピロカルピン)は白色の潮解性結晶．融点205 ℃．[α]D"＋91°(水)．アトロピンと反対の副交感神経作用をもち，緑内障治療に用いられる．LD50 119～151 mg/kg(マウス，経口)．[CAS 92-13-7][CAS 54-71-7:塩酸塩]
森北出版「化学辞典（第2版）
用途
コリン作動神経作用がある。緑内障治療に用いる
医薬用
中央・南アメリカ原産のPilocarpus jaborandiの葉から抽出されたアルカロイドで、その塩酸塩（塩酸ピロカルピン）が医薬品として用いられる。副交感神経作用薬で、縮瞳(しゅくどう)、唾液(だえき)分泌亢進(こうしん)、発汗、消化液分泌亢進、気管支分泌増大、消化管運動亢進、子宮・膀胱(ぼうこう)・胆管・気管支筋の収縮をおこす。アトロピンと拮抗(きっこう)する。塩酸ピロカルピンは無色の結晶または白色の粉末で無臭、味はわずかに苦い。毒薬で、製剤は劇薬。普通，塩酸塩として唾液分泌促進，発汗，瞳孔縮小などの目的に用いる。またアトロピン中毒の解毒にも使う。点眼液および眼軟膏(なんこう)として診断または治療のための縮瞳を目的とし、眼圧を低下させるので緑内障の治療に用いる。［幸保文治］
効能
抗緑内障薬, ムスカリン受容体作動薬
説明
Pilocarpine acts by stimulating muscarinic receptors, therefore making it similar in action
to acetylcholine when systematically introduced. This compound differs from acetylcholine in that it does not react with any nicotinic receptors, but by stimulating the CNS.
Its effects are blocked by atropine. It has found therapeutic use in ophthalmology as a
myotic agent.
化学的特性
Colorless crystalline solid or an oil; melts at34°C (93.2°F); dissolves in water, alcohol,and chloroform; slightly soluble in ether andbenzene.
物理的性質
Appearance: colorless crystal or white crystalline powder. Solubility: freely soluble
in water; slightly soluble in ethanol; insoluble in chloroform or diethyl ether.
Melting point: 174–178?°C.
来歴
It has a history of hundreds of years since pilocarpine was used to treat glaucoma
.
In 1933, the chemical synthesis of pilocarpine was firstly reported. However,
pilocarpine couldn’t be used for treatments, because its synthetic route is so long
and focuses on isopilocarpine, of which the pharmacological activities are 1/20–
1/50 of pilocarpine. In 1972, DeGraw successfully synthesized the cis-homopilopic
acid employing catalytic hydrogenation of precious metals and obtained pilocarpine
as the main part product. Therefore, the study on the production of pilocarpine by
chemical synthesis has made new progress and has been artificially synthesized .
使用
Pilocarpine occurs in the leaves of variousspecies of pilocarpus. It is used as an antidotefor atropine poisoning and in ophthalmologyto produce contraction of the pupil.
定義
ChEBI: The (+)-enantiomer of pilocarpine.
健康ハザード
Pilocarpine is a tropane alkaloid. Toxicsymptoms are characterized by muscariniceffects. Toxic effects include hypersecretionof saliva, sweat, and tears; contraction of thepupils of the eyes; and gastric pain accom panied with nausea, vomiting, and diarrhea.Other symptoms are excitability, twitching,and lowering of blood pressure. High dosesmay lead to death due to respiratory failure.A lethal dose in humans is estimated withinthe range of 150–200 mg.
薬理学
Pilocarpine activates cholinergic M-receptor and has an obvious effect on eyes and
salivary glands. Pilocarpine nitrate eye drops take part in the actions of myosis,
depressing intraocular pressure and alleviating cyclospasm. It increases glandular
secretions at 10–20? mg, i.h., including the sweat gland, salivary gland, lacrimal
gland, gastric gland, pancreas, intestinal gland, respiratory mucosa, and so on.
Pilocarpine activates intestinal smooth muscle and promotes its tension and peristalsis. It induces asthma by activating bronchial smooth muscle and activates
smooth muscles of uterus, bladder, gallbladder, and biliary passage as well
臨床応用
Pilocarpine nitrate is mainly used to treat glaucoma clinically. Characterized with
the progressive cupping of the optic disk, hypopsia, and elevated intraocular pressure, the severe patients will go blind. Patients with angle-closure glaucoma (congestive glaucoma) generally have the narrow anterior chamber angle, the obstruction
of aqueous humor outflow, and the elevation of intraocular pressure, and these can
be reversed by a low-concentration pilocarpine. But it is noted that a highconcentration pilocarpine will promote the progress of glaucoma. Pilocarpine is
also used to treat open-angle glaucoma. The mechanism of the action is not entirely
clear. Using atropine and pilocarpine alternately prevents posterior synechiae. In
addition, pilocarpine is orally used to treat Zagari’s disease after neck radiotherapy,
increasing salivary secretion and sweat secretion
安全性プロファイル
A human poison by
subcutaneous route. Poison experimentally
by ingestion, intravenous, intraperitoneal,
and subcutaneous routes. A very poisonous
alkaloid that is used to remove excess fluid
accumulations from the body. Its action on
the sweat glands makes it a powerful
sudorific. It very rarely causes death, but,
when it does, it is by paralysis of the heart or
edema of the lungs. Dangerous; on heating
to decomposition it emits toxic fumes of
NOx.
参考文献
Hardy., Bull. Soc. Chim. Fr., 24,497 (1875)
Gerrard., Pharm. J., 5,865,965 (1875)
Gerrard., ibid, 7,255 (1877)
Hardy, Calmels., Compt. rend., 102,1116,1251,1562 (1886)
Wagenaar., Pharm. Weekbl., 67, 285 (1930)
Preobrashenski et al., Ber., 63,460 (1930)
Preobrashenskietal., ibid, 69, 1835 (1936)
Roche, Lynch., Analyst, 73,311 (1948)
Pharmacology:
Hollander., Gastroenterology, 2, 20 I (1944)
ピロカルピン 上流と下流の製品情報
原材料
準備製品