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
Efffect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig.	2001	12162581
Detection of non-prescription heroin markers in urine with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.	2001 Sep	11550816
Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis.	2002 Jul 1	12085264
[Influence of fertilizers on yield and yield components of opium from Papaver somniferum Linn].	2003	14740399
HPLC determination of aminophylline, methoxyphenamine hydrochloride, noscapine and chlorphenamine maleate in compound dosage forms with an aqueous-organic mobile phase.	2003 Sep 15	12946529
Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats.	2004 Jul-Sep	15537167
PIKE GTPase signaling and function.	2005	15951849
Discovery of S-phase arresting agents derived from noscapine.	2005 Apr 21	15828811
Yeast DEL assay detects clastogens.	2005 Apr 4	15781217
Targeting microtubules for cancer chemotherapy.	2005 Jan	15720262
Development and validation of a capillary electrophoresis method for the determination of codeine, diphenhydramine, ephedrine and noscapine in pharmaceuticals.	2005 Jan	15652374
Automated multiple development thin-layer chromatography for separation of opiate alkaloids and derivatives.	2005 Jul 8	16008057
Simultaneous determination of methylephedrine and noscapine in human plasma by liquid chromatography-tandem mass spectrometry.	2005 Jun 25	15899371
Simultaneous determination of ingredients in a cold medicine by cyclodextrin-modified microemulsion electrokinetic chromatography.	2005 Mar 9	15740912
Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivars.	2005 May	15921406
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
Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog.	2006 Dec 15	17008104
Quantitative analysis of morphine and noscapine using corona discharge ion mobility spectrometry with ammonia reagent gas.	2006 Jun 15	18970639
Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro.	2006 May	16630910
p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells.	2007 Apr 15	17440101
Apoptotic pathway induced by noscapine in human myelogenous leukemic cells.	2007 Nov	17893514
Fatal poisoning by alcohol and heroin.	2007 Sep	17913687
Antitumor activity of noscapine in human non-small cell lung cancer xenograft model.	2008 Dec	18338172
Noscapine may increase the effect of warfarin.	2008 Feb	17875192
9-bromonoscapine-induced mitotic arrest of cigarette smoke condensate-transformed breast epithelial cells.	2009 Apr 15	19229861
Relevance of an opioid, noscapine in reducing cystogeneses in rat experimental model of polycystic ovary syndrome.	2009 Nov	19609106
General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: applications and constraints.	2009 Sep	19697309

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