ノスカピン

解説

ナルコチン．ノスカピンともいう．アヘン中に3～10％ 含まれるイソキノリンアルカロイドの一つ．融点176 ℃．密度1.395 g cm－3．[α]_D－147°(ベンゼン)．クロロホルムに易溶，ベンゼン，アセトンに可溶，エタノール，水に難溶．塩酸塩(融点220～225 ℃)は水溶性の無色の結晶で，麻酔作用は弱く，鎮咳作用が強い．合成品のdl-ナルコチンはグノスコピン(CAS 6035-40-1)とよばれる．LD50 83 mg/kg(ネズミ，静注)．

用途

各種の呼吸器疾患時の鎮咳薬

効能

鎮咳薬

商品名

ノスカピン (小堺製薬)

説明

A major constituent of opium (Papaver sornni!erurn), this phthalideisolquinoline base was probably first discovered by Derosne, but initially characterized by Robiquet who gave it the formula C23H3S0 7N, changed to that now accepted by Matthiesen and Foster. It crystallizes in colourless needles from EtOH and has [α]_D - 198° (c 1.0, CHC13); - 146° (c 2.0, toluene); - 147° (c 1.59, C6H6) and + 50° (1 % HCl). The alkaloid is a weak, monoacidic, tertiary base, forming unstable salts with acids which are dissociated with H20. The hydrochloride crystallizes with varying amounts of H20, is very soluble in water, readily decomposing into basic salts on standing. The platinichloride is amorphous; the oxalate has m.p. 174°C;[α]²⁰_D + 39.5° (H20); the phthalate, m.p. 160°C; [α]²²_D + 115° (CHC13); sesquisulphate, colourless crystals of the hexahydrate and the picrate, m.p. 1 74-S°C. The (+)-bromocamphorsulphonate has m.p. 110- 120°C; [α]_D + 100.7° (CHC13) and the corresponding (-)-bromocamphorsul_x0002_phonate, m.p. l80.SoC; [α]_D + 29° (CHC13). The alkaloid yields an N-oxide which is a hygroscopic solid; [α]_D + 135° (CHC13) furnishing a crystalline hydrochloride, m.p. 193°C; platinichloride, m.p. 175°C and a picrate, m.p. 130°C.
The base is unstable to heat and when heated in a sealed tube yields a mixture of dimethylnornarcotine, methylnornarcotine and nornarcotine. On heating with H20 and 150°C, or on boiling with dilute acids, it is hydrolyzed to opianic acid and hydrocotarnine. Similar degradations are brought about by acid oxidation orreduction, e.g. Zn and dilute HCl gives hydrocotarnine and meconin while dilute HN03 yields cotarnine and opianic acid. Pharmacologically, narcotine resembles thebaine (q.v.) in its action, being a reflex stimulant rather than a narcotic.

化学的特性

Crystalline Solid

定義

ChEBI: A benzylisoquinoline alkaloid that is 1,2,3,4-tetrahydroisoquinoline which is substituted by a 4,5-dimethoxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl group at position 1, a methylenedioxy group at positions 6-7 and a methoxy group at position 8. Obtained from p ants of the Papaveraceae family, it lacks significant painkilling properties and is primarily used for its antitussive (cough-suppressing) effects.

世界保健機関（WHO）

Noscapine, a centrally-acting cough suppressant and one of several alkaloids present in papaveretum (opium concentrate) was introduced into medicine many years ago. Subsequently, it was shown to increase the number of chromosomes in mammalian cell lines maintained in vitro. Although the clinical significance of this finding is uncertain, restrictive action was taken in a few countries since the possibility of a genotoxic effect cannot be excluded. On 4 December 1992 the European Committee on Proprietary Medicinal Products concluded that the available evidence does not indicate that use of noscapine holds any significant hazard. The Swedish Medical Products Agency also concluded that there is no justification to restrict the use of noscapine in women of childbearing age.

生物学の機能

Noscapine is a naturally occurring product of the opium poppy. It is a benzylisoquinoline with no analgesic or other CNS effects. Its antitussive effects are weak, but it is used in combination with other agents in mixtures for cough relief.

危険性

Narcotic, use legally restricted.

安全性プロファイル

Moderately toxic by ingestion andsubcutaneous routes. Mutation data reported. Anantitussive. When heated to decomposition it emits toxicfumes of NOx.

参考文献

Robiquet., Ann. Chim. Phys., 5,275 (1817)
Matthiessen, Foster.,!. Chern. Soc., 16,342 (1863)
Perkin, Robinson., ibid, 99,775 (1911)
Polonovski, Polonovski., Bull. Soc. Chim. Fr., 47, 361 (1930)
Lovell., Acta Cryst., 6, 869 (1953)
Barnes., Can. f. Chern., 33,444 (1955)
Safe, Moir., ibid, 160 (1964)
Stereochemistry: Battersby, Spenser., Tetrahedron Lett., 11 (1964)