NOSCAPINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H23NO7.ClH
Molecular Weight	449.881
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=MFLVZFXCSKVCSH-URBRKQAFSA-N

InChI=1S/C22H23NO7.ClH/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;1H/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
The significance of putative urinary markers of illicit heroin use after consumption of poppy seed products.	2006 Aug	16885724
Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death.	2006 Aug 14	16780803
Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog.	2006 Dec 15	17008104
Anxiolytic effect of noscapine in mice.	2006 Jul-Aug	16963805
Coated wire potentiometric detection for capillary electrophoresis studied using organic amines, drugs, and biogenic amines.	2006 Jun 1	16737236
Quantitative analysis of morphine and noscapine using corona discharge ion mobility spectrometry with ammonia reagent gas.	2006 Jun 15	18970639
Interaction of papaverine with the enalapril-induced cough in guinea pig.	2006 Mar	16830695
Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro.	2006 May	16630910
Synthesis and in vitro cytotoxicity of haloderivatives of noscapine.	2006 Oct 1	16784870
Treatment of hormone-refractory breast cancer: apoptosis and regression of human tumors implanted in mice.	2006 Sep	16985071
p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells.	2007 Apr 15	17440101
A simple and rapid flow-injection chemiluminescence method for the determination of noscapine with Ru(phen)3(2+)-Ce(IV) system.	2007 Aug	17899875
Optimum conditions for detecting hepatic micronuclei caused by numerical chromosome aberration inducers in mice.	2007 Aug 15	17561434
Differentiation of opium and poppy straw using capillary electrophoresis and pattern recognition techniques.	2007 Dec 12	18022406
Validation of meconin as a marker for illicit opiate use.	2007 Mar	17536746
Separation and determination of five major opium alkaloids with mixed mode of hydrophilic/cation-exchange monolith by pressurized capillary electrochromatography.	2007 Nov	17960847
Apoptotic pathway induced by noscapine in human myelogenous leukemic cells.	2007 Nov	17893514
Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent.	2007 Nov	17285314
Simultaneous voltammetric determination of morphine and noscapine by adsorptive differential pulse stripping method and least-squares support vector machines.	2007 Nov 30	18371637
Fatal poisoning by alcohol and heroin.	2007 Sep	17913687
Role of CAP350 in centriolar tubule stability and centriole assembly.	2008	19052644
Persistence of DNA threads in human anaphase cells suggests late completion of sister chromatid decatenation.	2008 Apr	17989990
Applicability of ultra-performance liquid chromatography-tandem mass spectrometry for heroin profiling.	2008 Apr 25	18374345
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
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.	2008 Dec	18493746
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
Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures.	2008 Jan 22	18211706
Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway.	2008 Jul	18525314
Warfarin-noscapine interaction: a series of four case reports.	2008 Mar	18303135
Noscapine inhibits human prostate cancer progression and metastasis in a mouse model.	2008 Nov-Dec	19189652
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 Apr	19067385
9-bromonoscapine-induced mitotic arrest of cigarette smoke condensate-transformed breast epithelial cells.	2009 Apr 15	19229861
Simultaneous determination of codeine and noscapine by flow-injection chemiluminescence method using N-PLS regression.	2009 Feb 20	19081219
The anti-cancer activity of noscapine: a review.	2009 Jan	19149691
[Noscapine and warfarin--a potentially dangerous interaction].	2009 Mar 12	19282895
Capillary zone electrophoresis with diode-array detection for analysis of local anaesthetics and opium alkaloids in urine samples.	2009 Mar 15	19249254
Tubulin-interactive natural products as anticancer agents.	2009 Mar 27	19125622
Validation of a liquid chromatography-tandem mass spectrometric assay for the quantitative determination of hydrastine and berberine in human serum.	2009 May 1	19269122
[Pharmacological treatment of acute cough].	2009 May 14	19448753
A validated hybrid quadrupole linear ion-trap LC-MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths.	2009 May 30	19297106
Recent patents reveal microtubules as persistent promising target for novel drug development for cancers.	2009 Nov	19673697
Relevance of an opioid, noscapine in reducing cystogeneses in rat experimental model of polycystic ovary syndrome.	2009 Nov	19609106
EM011 activates a survivin-dependent apoptotic program in human non-small cell lung cancer cells.	2009 Oct 30	19878573
General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: applications and constraints.	2009 Sep	19697309
Simultaneous chemiluminescence determination of thebaine and noscapine using support vector machine regression.	2010 Feb	20042361
Inclusion complexes of noscapine in beta-cyclodextrin offer better solubility and improved pharmacokinetics.	2010 Feb	19597818
Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.	2010 Feb 11	20161797
Simultaneous liquid chromatography-mass spectrometry quantification of urinary opiates, cocaine, and metabolites in opiate-dependent pregnant women in methadone-maintenance treatment.	2010 Jan-Feb	20109298

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 HYDROCHLORIDE

Common Name

English

NOSCAPINE HYDROCHLORIDE [EP IMPURITY]

Common Name

English

NOSCAPINI HYDROCHLORIDUM ANHYDROUS [WHO-IP LATIN]

Common Name

English

NOSCAPINE HCL

Common Name

English

NOSCAPINE (AS HYDROCHLORIDE)

Common Name

English

NOSCAPINE HYDROCHLORIDE ANHYDROUS [WHO-IP]

Common Name

English

NOSCAPINE HYDROCHLORIDE [MART.]

Common Name

English

Noscapine hydrochloride [WHO-DD]

Common Name

English

NOSCAPINE HYDROCHLORIDE [MI]

Common Name

English

NSC-757235

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C221