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

COC1=CC=C2[C@H](OC(=O)C2=C1OC)[C@@H]3N(C)CCC4=C3C(OC)=C5OCOC5=C4

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 20 Target ID: CHEMBL1881 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=24492608	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Cough 106 Sources: http://druginfosys.com/Drug.aspx?drugCode=1273&drugName=	Primary	Approved 8583	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00912899	Primary	Phase I 438	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 81 Sources: https://clinicaltrials.gov/ct2/show/NCT00183950	Primary	Phase II 1147	Unknown Approved Use Unknown
Chronic lymphocytic leukemia 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00183950	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
36.8 μg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/38809387/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
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
57 μg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/38809387/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
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
8.42 h REVIEW https://pubmed.ncbi.nlm.nih.gov/38809387/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		NOSCAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
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 Health Status: unhealthy Age Group: 57 years Sex: M 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 Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/	unhealthy, mean age 71 years Health Status: unhealthy Age Group: mean age 71 years Sex: F 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 Health Status: unhealthy Age Group: 57 years Sex: M 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 Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/	unhealthy, mean age 71 years Health Status: unhealthy Age Group: mean age 71 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/18303135/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438 substrate 1193	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 CYP2A6 879 CYP2E1 1060 CYP2C8 1057	CYP1A 26 CYP3A5 446 CYP2C19 1119 CYP3A4/5 91

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP3A4 2633	inhibitor 4027 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 2497	inhibitor 4027 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 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [IC50 100 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20233183/	yes [Inhibition 100 uM]
CYP1A2 2333	inhibitor 4027 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 2141	inhibitor 4027 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 26	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP2C19 1119	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP2C9 1193	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP3A4/5 91	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes
CYP3A5 446	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504993/	yes

PubMed

Title	Date	PubMed
Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.	2010-02-11	20161797
Simultaneous chemiluminescence determination of thebaine and noscapine using support vector machine regression.	2010-02	20042361
Inclusion complexes of noscapine in beta-cyclodextrin offer better solubility and improved pharmacokinetics.	2010-02	19597818
Simultaneous liquid chromatography-mass spectrometry quantification of urinary opiates, cocaine, and metabolites in opiate-dependent pregnant women in methadone-maintenance treatment.	2010-01-30	20109298
Recent patents reveal microtubules as persistent promising target for novel drug development for cancers.	2009-11	19673697
Relevance of an opioid, noscapine in reducing cystogeneses in rat experimental model of polycystic ovary syndrome.	2009-11	19609106
EM011 activates a survivin-dependent apoptotic program in human non-small cell lung cancer cells.	2009-10-30	19878573
General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: applications and constraints.	2009-09	19697309
A validated hybrid quadrupole linear ion-trap LC-MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths.	2009-05-30	19297106
[Pharmacological treatment of acute cough].	2009-05-14	19448753
Validation of a liquid chromatography-tandem mass spectrometric assay for the quantitative determination of hydrastine and berberine in human serum.	2009-05-01	19269122
9-bromonoscapine-induced mitotic arrest of cigarette smoke condensate-transformed breast epithelial cells.	2009-04-15	19229861
Adulterant profile of illicit street heroin and reduction of its precipitated physical dependence withdrawal syndrome by extracts of St John's wort (Hypericum perforatum).	2009-04	19067385
Tubulin-interactive natural products as anticancer agents.	2009-03-27	19125622
Capillary zone electrophoresis with diode-array detection for analysis of local anaesthetics and opium alkaloids in urine samples.	2009-03-15	19249254
[Noscapine and warfarin--a potentially dangerous interaction].	2009-03-12	19282895
Simultaneous determination of codeine and noscapine by flow-injection chemiluminescence method using N-PLS regression.	2009-02-20	19081219
Noscapine inhibits human prostate cancer progression and metastasis in a mouse model.	2009-02-05	19189652
The anti-cancer activity of noscapine: a review.	2009-01	19149691
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008-12	18493746
Antitumor activity of noscapine in human non-small cell lung cancer xenograft model.	2008-12	18338172
Antiangiogenic effects of noscapine enhance radioresponse for GL261 tumors.	2008-08-01	18640497
Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro.	2008-08	18766974
Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway.	2008-07	18525314
Applicability of ultra-performance liquid chromatography-tandem mass spectrometry for heroin profiling.	2008-04-25	18374345
Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation.	2008-04	17989990
Warfarin-noscapine interaction: a series of four case reports.	2008-03	18303135
Noscapine may increase the effect of warfarin.	2008-02	17875192
Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures.	2008-01-22	18211706
Role of CAP350 in centriolar tubule stability and centriole assembly.	2008	19052644
Differentiation of opium and poppy straw using capillary electrophoresis and pattern recognition techniques.	2007-12-12	18022406
Simultaneous voltammetric determination of morphine and noscapine by adsorptive differential pulse stripping method and least-squares support vector machines.	2007-11-30	18371637
Separation and determination of five major opium alkaloids with mixed mode of hydrophilic/cation-exchange monolith by pressurized capillary electrochromatography.	2007-11	17960847
Apoptotic pathway induced by noscapine in human myelogenous leukemic cells.	2007-11	17893514
Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent.	2007-11	17285314
Fatal poisoning by alcohol and heroin.	2007-09	17913687
Optimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice.	2007-08-15	17561434
A simple and rapid flow-injection chemiluminescence method for the determination of noscapine with Ru(phen)3(2+)-Ce(IV) system.	2007-08	17899875
p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells.	2007-04-15	17440101
Validation of meconin as a marker for illicit opiate use.	2007-03	17536746
Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog.	2006-12-15	17008104
Synthesis and in vitro cytotoxicity of haloderivatives of noscapine.	2006-10-01	16784870
Treatment of hormone-refractory breast cancer: apoptosis and regression of human tumors implanted in mice.	2006-09	16985071
Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death.	2006-08-14	16780803
The significance of putative urinary markers of illicit heroin use after consumption of poppy seed products.	2006-08	16885724
Quantitative analysis of morphine and noscapine using corona discharge ion mobility spectrometry with ammonia reagent gas.	2006-06-15	18970639
Coated wire potentiometric detection for capillary electrophoresis studied using organic amines, drugs, and biogenic amines.	2006-06-01	16737236
Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro.	2006-05	16630910
Interaction of papaverine with the enalapril-induced cough in guinea pig.	2006-03	16830695
Anxiolytic effect of noscapine in mice.	2005-12-07	16963805

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

NARCOTINUM

Preferred Name

English

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

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