Noscapine

Structural formula
General
Non-proprietary name	Noscapine
other names	(-) - Narcotine; α-Gnoscopine (racemate); Methoxy hydrastine ; (3 S ) -6,7-Dimethoxy-3 - [(5 R ) -5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo [4.5 g ] isoquinoline -5-yl] -1 (3 H ) -isobenzofuranone;
Molecular formula	C 22 H 23 NO 7
Brief description	white crystals
External identifiers / databases
EC number	204-899-2
ECHA InfoCard	100.004.455
PubChem	4544
ChemSpider	4385
Wikidata	Q415619
Drug information
ATC code	R05 DA07
Drug class	Antitussive
properties
Molar mass	413.42 g mol −1
Physical state	firmly
Melting point	176 ° C
solubility	slightly soluble in water (300 mg l −1 at 30 ° C); soluble in acetone , glacial acetic acid , chloroform and ethanol ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	853 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Noscapine is the international non-proprietary name for (-) - α-narcotine , a main alkaloid of opium (3–10%), which is used as a drug for coughing ( antitussive ). The ten genes responsible for biosynthesis in the opium poppy ( Papaver somniferum ) have been identified.

Opium poppy, Papaver somniferum , from whose milk noscapine can be obtained.

The compound was known to Antoine Baumé as opium extract as early as 1762 (and later Charles Derosne in the salt named after him) and was isolated from opium by Pierre-Jean Robiquet in 1817 . It has a structure derived from 1-benzyl-1,2,3,4-tetrahydroisoquinoline; as a pure substance, it forms colorless prisms . It is chemically a methoxy derivative of hydrastine .

The molecule contains two centers of chirality , so that four stereoisomers exist. The natural, enantiomerically pure (-) - α-form is used medicinally .

Stereoisomers of noscapine
(-) - α-noscapine	(3 S , 5 R )	erythro shape
(+) - α-noscapine	(3 R , 5 S )	erythro shape
(-) - β-noscapine	(3 rows , 5 rows )	threo shape
(+) - β-noscapine	(3 S , 5 S )	threo shape

During the oxidative breakdown of noscapine, the breakdown products cotarnine and opianic acid are formed . Methylation of the nitrogen atom to the quaternary ammonium ion , conversion into the hydroxide and heating (analogous to Hofmann degradation ) results in narceine .

(-) - α-Noscapine has an antitussive, but not pain-relieving effect, although the effect is somewhat weaker than that of codeine . In contrast to morphine, noscapine has a weak respiratory stimulus and bronchodilator effect . Noscapine also inhibits mitosis , specifically in tumor cells, making it a potential anti-cancer agent.

The plasma half-life of noscapine is 2.6 to 4.5 hours. The bioavailability is individually variable and is around 30%. There are no known serious side effects.

Trade names

Monopreparations

Capval (D), Tussanil N (CH), Nosca-Mereprin (B, L)

Combination preparations

DemoTussil (CH), Hederix (CH), Tossamin (CH), Tuscalman (A)

Individual evidence

↑ ^a ^b ^c ^d Entry on (-) - α-narcotine. In: Römpp Online . Georg Thieme Verlag, accessed on April 19, 2014.
↑ ^a ^b ^c Entry on noscapine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b Data sheet (S, R) -Noscapine from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).
↑ T. Winzer, V. Gazda u. a .: A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine. In: Science. 336, 2012, pp. 1704-1708, doi : 10.1126 / science.1220757 .
↑ Winfried Pötsch u. a. Lexicon of important chemists , Harri Deutsch 1989, Baumé article
↑ K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 7.1, noscapine. Loose-leaf collection, 40th delivery 2012, Wissenschaftliche Verlagsgesellschaft Stuttgart.
^ Harry Auterhoff , Textbook of Pharmaceutical Chemistry, Wissenschaftliche Verlagsgesellschaft Stuttgart, 1968.
↑ M. Mahmoudian, P. Rahimi-Moghaddam: The anti-cancer activity of noscapine: a review. In: Recent Patents on Anti-Cancer Drug Discovery . Volume 4, Number 1, January 2009, pp. 92-97, PMID 19149691 . (Review).
↑ Holz, Schwabe et al .: Pocket book of drug treatment: Angewandte Pharmakologie , 13th edition; Springer-Verlag; Berlin, Heidelberg 2005. ISBN 3-540-20821-6 .
↑ Ernst Mutschler, Monika Schäfer-Korting: Textbook of Pharmacology and Toxicology . 8th, completely revised and expanded edition. Wissenschaftliche Verlagsgesellschaft Stuttgart 2001. ISBN 3-8047-1763-2 . P. 224.

[roempp-1] Entry on (-) - α-narcotine. In: Römpp Online . Georg Thieme Verlag, accessed on April 19, 2014.

[ChemIDplus-2] Entry on noscapine in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Sigma-3] Data sheet (S, R) -Noscapine from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

[DOI10.1126/science.1220757-4] T. Winzer, V. Gazda u. a .: A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine. In: Science. 336, 2012, pp. 1704-1708, doi : 10.1126 / science.1220757 .

[5] Winfried Pötsch u. a. Lexicon of important chemists , Harri Deutsch 1989, Baumé article

[6] K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 7.1, noscapine. Loose-leaf collection, 40th delivery 2012, Wissenschaftliche Verlagsgesellschaft Stuttgart.

[7] Harry Auterhoff , Textbook of Pharmaceutical Chemistry, Wissenschaftliche Verlagsgesellschaft Stuttgart, 1968.

[8] M. Mahmoudian, P. Rahimi-Moghaddam: The anti-cancer activity of noscapine: a review. In: Recent Patents on Anti-Cancer Drug Discovery . Volume 4, Number 1, January 2009, pp. 92-97, PMID 19149691 . (Review).

[9] Holz, Schwabe et al .: Pocket book of drug treatment: Angewandte Pharmakologie , 13th edition; Springer-Verlag; Berlin, Heidelberg 2005. ISBN 3-540-20821-6 .

[10] Ernst Mutschler, Monika Schäfer-Korting: Textbook of Pharmacology and Toxicology . 8th, completely revised and expanded edition. Wissenschaftliche Verlagsgesellschaft Stuttgart 2001. ISBN 3-8047-1763-2 . P. 224.