NOSCAPINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H23NO7
Molecular Weight	413.4205
Optical Activity	( - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(OC(=O)C2=C1C=CC(OC)=C2OC)[C@]3([H])N(C)CCC4=CC5=C(OCO5)C(OC)=C34

InChI

InChIKey=AKNNEGZIBPJZJG-MSOLQXFVSA-N

InChI=1S/C22H23NO7/c1-23-8-7-11-9-14-20(29-10-28-14)21(27-4)15(11)17(23)18-12-5-6-13(25-2)19(26-3)16(12)22(24)30-18/h5-6,9,17-18H,7-8,10H2,1-4H3/t17-,18+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://druginfosys.com/Drug.aspx?drugCode=1273&drugName=
Curator's Comment: description was created based on several sources, including http://www.jbc.org/content/289/11/7505.full.pdf+html https://en.wikipedia.org/wiki/Noscapine http://www.pnas.org/content/95/4/1601.full

Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid from plants of the poppy family, without painkilling properties. This agent is primarily used for its antitussive (cough-suppressing) effects. Noscapine is often used as an antitussive medication. A 2012 Dutch guideline, however, does not recommend its use for coughing. Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased. Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation. Mechanisms for its antitussive action are unknown, although animal studies have suggested central nervous system as a site of action. Furthermore, noscapine causes apoptosis in many cell types and has potent antitumor activity against solid murine lymphoid tumors (even when the drug was administered orally) and against human breast and bladder tumors implanted in nude mice. Because noscapine is water-soluble and absorbed after oral administration, its chemotherapeutic potential in human cancer merits thorough evaluation. Antifibrotic effect of noscapine based on novel mechanism, which it shows through EP2 prostaglandin E2 receptor-mediated activation of protein kinase A.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostanoid EP2 receptor 19 Target ID: CHEMBL1881 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=24492608	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Cough 106 Sources: http://druginfosys.com/Drug.aspx?drugCode=1273&drugName=	Primary	Approved 8429	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00912899	Primary	Phase I 428	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: https://clinicaltrials.gov/ct2/show/NCT00183950	Primary	Phase II 1132	Unknown Approved Use Unknown
Chronic lymphocytic leukemia 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00183950	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
394 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2257866	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
794 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2257866	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2257866	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
7% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1972403			NOSCAPINE serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 mg 1 times / day single, oral Studied dose Dose: 4 mg, 1 times / day Route: oral Route: single Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21342238/	unhealthy, 57 years n = 1 Health Status: unhealthy Condition: common cold Age Group: 57 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21342238/	Other AEs: Drug eruption... Other AEs: Drug eruption Sources: https://pubmed.ncbi.nlm.nih.gov/21342238/
50 mg 3 times / day multiple, oral Recommended Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Co-administed with:: Warfarin(mean dose 26 mg; 1 week) Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/	unhealthy, mean age 71 years n = 4 Health Status: unhealthy Condition: cough Age Group: mean age 71 years Sex: F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/	Other AEs: International normalized ratio increased... Other AEs: International normalized ratio increased Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/

AEs

AE	Significance	Dose	Population
Drug eruption		4 mg 1 times / day single, oral Studied dose Dose: 4 mg, 1 times / day Route: oral Route: single Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21342238/	unhealthy, 57 years n = 1 Health Status: unhealthy Condition: common cold Age Group: 57 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/21342238/
International normalized ratio increased		50 mg 3 times / day multiple, oral Recommended Dose: 50 mg, 3 times / day Route: oral Route: multiple Dose: 50 mg, 3 times / day Co-administed with:: Warfarin(mean dose 26 mg; 1 week) Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/	unhealthy, mean age 71 years n = 4 Health Status: unhealthy Condition: cough Age Group: mean age 71 years Sex: F Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767 substrate 1037	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP1A2 1524 CYP2A6 707 CYP2E1 882 CYP2C8 911	CYP1A 22 CYP3A5 395 CYP2C19 991 CYP3A4/5 85

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	strong [IC50 10.8 uM]	no (co-administration study) Comment: administered with quinine. See https://pubmed.ncbi.nlm.nih.gov/20668444/ Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	strong [IC50 13.3 uM]	yes (pharmacogenomic study) Comment: noscapine reduces CYP2C9 activity to the reported level in subjects with CYP2C92/3. Mean increase of losartan phenotypic index was 4.9 fold. See https://pubmed.ncbi.nlm.nih.gov/20668444/ Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [IC50 100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]	no (co-administration study) Comment: administered with caffeine. See https://pubmed.ncbi.nlm.nih.gov/20668444/ Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20668444/	yes	yes (co-administration study) Comment: Mean increase of omeprazole phenotypic index was 3.6 fold. Sources: https://pubmed.ncbi.nlm.nih.gov/20668444/

Drug as victim

Target	Modality	Activity
CYP1A 22	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP2C19 991	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP3A4/5 85	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP3A5 395	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes

PubMed

Title	Date	PubMed
Characterization of an unknown component in Noscapine using liquid chromatography-mass spectrometry and proton nuclear magnetic resonance spectroscopy.	2001 Aug 24	11572402
Sustained activation of p34(cdc2) is required for noscapine-induced apoptosis.	2001 Dec 14	11679575
Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a diagnostic pitfall.	2001 Feb	11235901
GC/MS determination of pyrolysis products from diacetylmorphine and adulterants of street heroin samples.	2002 Jul	12137001
Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine.	2002 Oct 18	12183452
Use of dynamically coated capillaries with added cyclodextrins for the analysis of opium using capillary electrophoresis.	2003 Jan 10	12564681
Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric analysis of opiates and metabolites in rat urine after inhalation of opium.	2003 Jun 5	12726852
Measuring the mitotic index in chemically-treated human lymphocyte cultures by flow cytometry.	2003 Jun 6	12787817
Application of capillary zone electrophoresis in the separation and determination of the principal gum opium alkaloids.	2003 May	12731031
Noscapine hydrochloride-induced numerical aberrations in cultured human lymphocytes: a comparison of FISH detection methods and multiple end-points.	2003 May	12714688
HPLC determination of aminophylline, methoxyphenamine hydrochloride, noscapine and chlorphenamine maleate in compound dosage forms with an aqueous-organic mobile phase.	2003 Sep 15	12946529
Discovery of S-phase arresting agents derived from noscapine.	2005 Apr 21	15828811
Yeast DEL assay detects clastogens.	2005 Apr 4	15781217
Principal opium alkaloids as possible biochemical markers for the source identification of Indian opium.	2005 Aug	16158998
Simultaneous determination of methylephedrine and noscapine in human plasma by liquid chromatography-tandem mass spectrometry.	2005 Jun 25	15899371
A rapid and reliable solid-phase extraction method for high-performance liquid chromatographic analysis of opium alkaloids from papaver plants.	2005 Nov	16272729
Identification of novel and improved antimitotic agents derived from noscapine.	2005 Nov 17	16279766
Anxiolytic effect of noscapine in mice.	2006 Jul-Aug	16963805
Separation and determination of five major opium alkaloids with mixed mode of hydrophilic/cation-exchange monolith by pressurized capillary electrochromatography.	2007 Nov	17960847
Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent.	2007 Nov	17285314
Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation.	2008 Apr	17989990
Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro.	2008 Aug	18766974
Antiangiogenic effects of noscapine enhance radioresponse for GL261 tumors.	2008 Aug 1	18640497
Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway.	2008 Jul	18525314
[Noscapine and warfarin--a potentially dangerous interaction].	2009 Mar 12	19282895

Patents

Sample Use Guides

In Vivo Use Guide

25 to 50 mg 8 hourly

Route of Administration: Oral

In Vitro Use Guide

Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC(50)=75 μM). This cytotoxicity was reflected by cell cycle arrest at G(2)/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9

Name

Type

Language

NOSCAPINE

Official Name

English

NSC-5366

Code

English

1(3H)-ISOBENZOFURANONE, 6,7-DIMETHOXY-3-(5,6,7,8-TETRAHYDRO-4-METHOXY-6-METHYL-1,3-DIOXOLO(4,5-G)-ISOQUINOLIN-5-YL), (S-(R*,S*))-

Common Name

English

NARCOTINUM

Common Name

English

NOSCAPINE [MI]

Common Name

English

Narcotine

Common Name

English

NOSCAPINUM [WHO-IP LATIN]

Common Name

English

NOSCAPINE [JAN]

Common Name

English

NOSCAPINE [USP-RS]

Common Name

English

NOSCAPINE [WHO-IP]

Common Name

English

NOSCAPINE [USP MONOGRAPH]

Common Name

English

NOSCAPINE [HSDB]

Common Name

English

noscapine [INN]

Common Name

English

Noscapine [WHO-DD]

Common Name

English

NOSCAPINE [EP MONOGRAPH]

Common Name

English

(-)-NARCOTINE

Common Name

English

TUSSCAPINE

Common Name

English

(-)-.ALPHA.-NARCOTINE

Common Name

English

NARCOTINUM [HPUS]

Common Name

English

METHOXYHYDRASTINE

Common Name

English

NOSCAPINE [MART.]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

500615