Chemical Properties
Crystalline Solid
Uses
antiacne, antiproliferative agent
Definition
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.
Hazard
Narcotic, use legally restricted.
Description
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]20D
+ 39.5° (H20); the phthalate, m.p. 160°C;
[α]22D + 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.
Brand name
Tusscapine (Fisons);Bequitussin;Bisolvon compositum;Broncha-tulisan eucalyptol;Broncho-tulisan eucalyptol;Brosolin-rectocap;Codipect;Codyl cum expectoras;Coscotab;Degoran;Dettuso;Difimetus compositum;Finipect;Hederix;Lyabex retard;Nipaxan;Nitepax;Nosaclin;Noscalin;Noscapect;Noscarex;Noscatuss;Reatos;Rectolmin bronquial;Ribelfan;Stilco;Teletux;Tucotin;Tuscapin;Tussamine plus;Tussanil n;Tusscalman;Tussicure;Tussisedal;Tussoretard.
World Health Organization (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.
Biological Functions
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.
Safety Profile
Moderately toxic by ingestion andsubcutaneous routes. Mutation data reported. Anantitussive. When heated to decomposition it emits toxicfumes of NOx.
References
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)
