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{{Drugbox|
{{Drugbox
|IUPAC_name =  
| Verifiedfields = changed
| image =
| verifiedrevid = 408343932
| CAS_number=912-60-7
| IUPAC_name = (3''S'')- 6,7-Dimethoxy-3-[(5''R'')-5,6,7,8-tetrahydro- 4-methoxy- 6-methyl- 1,3-dioxolo (4,5-g)isoquinolin-5-yl]- 1(3H)-isobenzofuranone
| ATC_prefix=R05
| image = Narkotin - Narcotine.png
| ATC_suffix=DA07  
| image2 = Noscapine.png
| ATC_supplemental=
<!--Clinical data-->
| PubChem=4544
| tradename = 
| DrugBank=
| Drugs.com = {{drugs.com|international|noscapine}}
| C=22 | H=23 | N=1 | O=7
| pregnancy_category = Contraindicated
| legal_status = Rx-only
| routes_of_administration = 
 
<!--Pharmacokinetic data-->
| bioavailability = ~30%
| metabolism = 
| elimination_half-life = 1.5 to 4h (mean 2.5)
| excretion = 
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 128-62-1
| ATC_prefix = R05
| ATC_suffix = DA07
| PubChem = 275196
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 242139
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8V32U4AOQU
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 73237
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01036
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 364713
 
<!--Chemical data-->
| C=22 | H=23 | N=1 | O=7  
| molecular_weight = 413.421
| molecular_weight = 413.421
| bioavailability=  
| smiles = O=C2O[C@@H](c1ccc(OC)c(OC)c12)[C@@H]5N(C)CCc4c5c(OC)c3OCOc3c4
| metabolism =  
| InChI = 1/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
| elimination_half-life=
| InChIKey = AKNNEGZIBPJZJG-MSOLQXFVBO
| excretion =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =  
| StdInChI = 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
| legal_status =  
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration=  
| StdInChIKey = AKNNEGZIBPJZJG-MSOLQXFVSA-N
| synonyms = Narcotine
}}
}}
 
__Notoc__
{{SI}}
{{SI}}
 
{{CMG}}
 
==Overview==
==Overview==
'''Noscapine''' (also known as '''Narcotine''' or '''Anarcotine''') is an [[alkaloid]] [[opioid]] [[agonist]] from plants of the Papaveraceae family, without significant [[analgesic|painkilling]] properties.<ref>{{cite web |url=http://www.unodc.org/unodc/en/bulletin/bulletin_1959-01-01_2_page008.html |title=UNODC - Bulletin on Narcotics - 1959 Issue 2 - 007 |accessdate=2007-07-16 |format= |work=}}</ref>  It is grouped as part of the benzylisoquinolines, of which [[papaverine]] is also included.  This agent is primarily used for its [[antitussive]] (cough-suppressing) effects. It has also been shown to have anticancer activity ([http://www.ott.emory.edu/share/technologies/descriptions/97012.pdf PDF file]).
==Structure analysis==
Naturally it occurs as alpha enantiomer. It can be converted in the beta enantiomer when it is dissolved in alkaline water-ethanol solvutions.
The lacton ring is unstable and it opens in basic media. The oposit reaction is presented in acidic media.
The bond C1-C3' is unstable also. This is the bond connecting the two optical active carbon atoms. In water solution of sulphuric acid and heating it dissociats into Cortarnin (4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline) and Opic acid (6-formyl-2,3-dimethoxybenzoic acid). When Noscapine is reduced with Zn/HCl the bond C1-C3' saturates and the molecule dissociates into Hydrocortarin (2-hydroxycortarin) and Merconine (6,7-dimethoxyisobenzofuran-1(3H)-one).
==Mechanism of action==
Noscapine's antitussive effects appear to be primarily mediated by its [[Sigma receptor#The .CF.83 receptor|sigma receptor]] agonist activity.  Evidence for this mechanism is suggested by experimental evidence in rats.  Pretreatment with [[rimcazole]], a sigma specific [[antagonist]], causes a dose-dependent reduction in antitussive activity of noscapine.<ref name="pmid9232674">{{cite journal |author=Kamei J |title=Role of opioidergic and serotonergic mechanisms in cough and antitussives |journal=Pulmonary pharmacology |volume=9 |issue=5-6 |pages=349-56 |year=1996 |pmid=9232674 |doi=}}</ref>
==Cancer and stroke treatment==
Noscapine is currently under investigation for use in the treatment of several [[cancer]]s and hypoxic [[ischemia]] in [[stroke]] patients. In cancer treatment, noscapine appears to interfere with [[microtubule]] function, and thus the division of cancer cells in a way similar to the [[taxanes]]. Early studies in treatment of [[prostate cancer]] are very promising.<ref>{{cite web |url=http://www.news-medical.net/?id=21951 |title=Noscapine effective against prostate cancer |accessdate=2007-07-16 |format= |work=}}</ref>
In stroke patients, noscapine blocks the [[bradykinin]]e b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine.<ref>{{cite web |url=http://www.springerlink.com/content/dlp6jd6gvrtgauk3/ |title=A preliminary report on the application of noscapine in the treatment of stroke |accessdate=2007-07-16 |format= |work=}}</ref>
Studies are currently underway to assess the effectiveness of this drug in cancer and stroke treatment. Noscapine is non-addictive, widely available, has a low [[side-effect]] incidence, and is easily administered orally, thus it has great potential for use, especially in developing countries.


==Noscapine Abuse==
'''Noscapine''' (also known as '''Narcotine''', '''Nectodon''', '''Nospen''', '''Anarcotine''' and (archaic) '''Opiane''') is a [[benzylisoquinoline]] [[alkaloid]] from plants of the [[Papaveraceae|poppy family]], without [[analgesic|painkilling]] properties. This agent is primarily used for its [[antitussive]] (cough-suppressing) effects.
Noscapine (Nospen) has a history of [[Over-the-counter drug]] abuse in a several countries being readily available from local pharmacies as a prescription drug.
The effects, beginning around 45 to 120 mins after consumption, are similar to [[dextromethorphan]] and [[alcohol intoxication]].  Abuse of noscapine and other cough suppressants ([[dextromethorphan]], [[codeine]], [[antihistamines]], and [[xylometazoline]] nasal drops) has been reported to cause chronic cough lasting over one month upon withdrawal.<ref>{{cite web|url=http://www.jpps.com.pk/show_article.php?JID=1&ArtID=6|title=Pattern of drug abuse in patients with a psychogenic cough|author=M.S. Bhatia and Lakshi Vaid|year=2005|accessdate=2007-05-21}}</ref>  Unlike dextromethorphan, noscapine is not an [[NMDA receptor antagonist]].<ref>PMID 2673498</ref>


==Noscapine in Heroin==
Noscapine can survive the manufacturing processes of [[heroin]] and can be found in street heroin. This is useful for law enforcement agencies, as the amounts of contaminants can identify the source of seized drugs. In 2005 in Liege, Belgium, the average noscapine concentration was around 8%.<ref name="pmid16265967">{{cite journal |author=Denooz R, Dubois N, Charlier C |title=[Analysis of two year heroin seizures in the Liege area] |language=French |journal=Revue médicale de Liège |volume=60 |issue=9 |pages=724-8 |year=2005 |pmid=16265967 |doi=}}</ref>


Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed [[diamorphine]].<ref name="pmid16367984">{{cite journal |author=Paterson S, Lintzeris N, Mitchell TB, Cordero R, Nestor L, Strang J |title=Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence |journal=Addiction |volume=100 |issue=12 |pages=1832-9 |year=2005 |pmid=16367984 |doi=10.1111/j.1360-0443.2005.01225.x}}</ref> Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in [[urine]] samples alongside noscapine include [[papaverine]] and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine . Detection is usually by [[gas chromatography-mass spectrometry]] or Liquid Chromatography-Mass Spectrometry (LCMS) but can also use a variety of other analytical techniques.
==Medical uses==
Noscapine is often used as an [[antitussive]] medication.<ref>{{cite journal|last1=Singh|first1=H|last2=Singh|first2=P|last3=Kumari|first3=K|last4=Chandra|first4=A|last5=Dass|first5=SK|last6=Chandra|first6=R|title=A review on noscapine, and its impact on heme metabolism.|journal=Current drug metabolism|date=March 2013|volume=14|issue=3|pages=351-60|pmid=22935070}}</ref> A 2012 Dutch guideline; however, does not recommend its use for [[cough]]ing.<ref>{{cite journal|last1=Verlee|first1=L|last2=Verheij|first2=TJ|last3=Hopstaken|first3=RM|last4=Prins|first4=JM|last5=Salomé|first5=PL|last6=Bindels|first6=PJ|title=[Summary of NHG practice guideline 'Acute cough'].|journal=Nederlands tijdschrift voor geneeskunde|date=2012|volume=156|issue=0|pages=A4188|pmid=22917039}}</ref>


==Possible side-effects==
==Side effects==
*[[Loss of coordination]]
*[[Loss of coordination]]
*[[Hallucinations]] (auditory and visual)
*[[Hallucinations]] (auditory and visual)
*Loss of sexual drive
*[[Loss of sexual drive]]
*Swelling of prostate
*[[Swelling of prostate]]
*[[Loss of appetite]]
*[[Loss of appetite]]
*[[Dilated pupils]]
*[[Dilated pupils]]
*Increased heart rate
*[[Increased heart rate]]
*Shaking and [[muscle spasms]]
*[[Tremor|Shaking]] and [[muscle spasms]]
*Chest pains
*Increased alertness
*Increased alertness
*Loss of any sleepiness
*Loss of any sleepiness
*Loss of [[stereoscopic vision]]
*Loss of [[stereoscopic vision]]


The effects shown above are not permanent, the user may experience spasms the following day after yawning. It is possible to over dose (20+ pills) and avoid taking any other drug in combination to this medication.
== Interactions ==
Noscapine can increase the effects of centrally sedating substances such as alcohol and [[hypnotic]]s.<ref>{{cite book|title=Austria-Codex|editor=Jasek, W|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=2007/2008|isbn=978-3-85200-181-4|language=German}}</ref>
 
The drug should not be taken with any [[MAOI]]s (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.{{citation needed|date=February 2012}}
 
Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased.<ref>{{cite doi|10.1111/j.1365-2125.2007.03018.x}}</ref>
 
==Mechanism of action==
Noscapine's antitussive effects appear to be primarily mediated by its [[Sigma receptor#The σ receptor|σ–receptor]] agonist activity.  Evidence for this mechanism is suggested by experimental evidence in rats.  Pretreatment with [[rimcazole]], a σ- specific [[Receptor antagonist|antagonist]], causes a dose-dependent reduction in antitussive activity of noscapine.<ref name="pmid9232674">{{cite journal |author=Kamei J |title=Role of opioidergic and serotonergic mechanisms in cough and antitussives |journal=Pulmonary pharmacology |volume=9 |issue=5–6 |pages=349–356 |year=1996 |pmid=9232674 |doi=10.1006/pulp.1996.0046}}</ref>
 
==Structure analysis==
The [[lactone]] ring is unstable and opens in basic media. The opposite reaction is presented in acidic media.
The bond C1-C3' is also unstable. This is the bond connecting the two optically active carbon atoms. In aqueous solution of [[sulfuric acid]] and heating it dissociates into [[cotarnine]] (4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline) and [[opic acid]] (6-formyl-2,3-dimethoxybenzoic acid). When noscapine is reduced with [[zinc]]/[[HCl]], the bond C1-C3' saturates and the molecule dissociates into [[hydrocotarnine]] (2-hydroxycotarnine) and [[meconine]] (6,7-dimethoxyisobenzofuran-1(3''H'')-one).
==History==
Noscapine was first isolated and characterized in chemical breakdown and properties in 1817 under the denomination of "Narcotine"<ref>''Observations sur le mémoire de M. Sertuerner relatif à l’analyse de l’opium'', Robiquet,  Annales de Chimie et de Physique , volume 5 (1817), p275–278</ref> by [[Pierre Robiquet]], a French chemist in Paris. Robiquet conducted over 20 years between 1815 and 1835 a series of studies in the enhancement of methods for the isolation of [[morphine]], and also isolated in 1832 another very important component of raw opium, that he called [[codeine]], currently a  widely used opium-derived [[compound]].
 
==Society and culture==
===Recreational use===
There are anecdotal reports of the recreational use of [[over-the-counter drug]]s in several countries, being readily available from local pharmacies without a prescription.
The effects, beginning around 45 to 120 mins after consumption, are similar to [[dextromethorphan]] and [[alcohol intoxication]]. Unlike dextromethorphan, noscapine is not an [[NMDA receptor antagonist]].<ref>{{cite journal | pmid = 2673498 | volume=67 | issue=6 | title=Antitussive agents as N-methylaspartate antagonists: further studies |date=June 1989 | journal=Can. J. Physiol. Pharmacol. | pages=561–7 | author=Church J, Jones MG, Davies SN, Lodge D | doi=10.1139/y89-090}}</ref>


WARNING: Do not take noscapine with any [[MAOI]]s (monoamine oxidase inhibitors), unknown and potentially fatal effects may occur. There are no significant contraindications listed for this drug but caution should be exercised.
===Noscapine in heroin===
Noscapine can survive the manufacturing processes of [[heroin]] and can be found in street heroin. This is useful for law enforcement agencies, as the amounts of contaminants can identify the source of seized drugs. In 2005 in Liège, [[Belgium]], the average noscapine concentration was around 8%.<ref name="pmid16265967">{{cite journal |author=Denooz R, Dubois N, Charlier C |title=[Analysis of two year heroin seizures in the Liege area] |language=French |journal=Revue médicale de Liège |volume=60 |issue=9 |pages=724–8 |year=2005 |pmid=16265967 |doi=}}</ref>


==References==
Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed [[diamorphine]].<ref name="pmid16367984">{{cite journal |author=Paterson S, Lintzeris N, Mitchell TB, Cordero R, Nestor L, Strang J |title=Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence |journal=[[Addiction (journal)|Addiction]] |volume=100 |issue=12 |pages=1832–1839 |year=2005 |pmid=16367984 |doi=10.1111/j.1360-0443.2005.01225.x}}</ref>  Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in [[urine]] samples alongside noscapine include [[papaverine]] and [[acetylcodeine]]. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, [[cotarnine]] and [[meconine]]. Detection is performed by [[gas chromatography-mass spectrometry]] or liquid chromatography-mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
{{Reflist|2}}


==External links==
==Research==
* [http://www.pcref.org/MedInsight%20-%20PCREF%20Noscapine%20Review.pdf Noscapine, A safe cough suppressant with newly discovered effects in treating cancer and stroke.]
Noscapine is currently being investigated as an antitumor agent in animal models of several human cancers.


{{pharma-stub}}
== See also ==
{{Cough and cold preparations}}
* [[Narceine]], a lesser known but related opium alkaloid.
[[Category:Sigma agonists]]
[[Category:Antitussives]]


== References ==
{{Reflist|2}}


{{Cough and cold preparations}}
{{Hallucinogens}}


{{WH}}


{{WS}}
[[Category:Natural opium alkaloids]]
[[Category:Antitussives]]
[[Category:Lactones]]
[[Category:Phenol ethers]]
[[Category:Sigma agonists]]

Latest revision as of 18:56, 8 April 2015

Noscapine
Clinical data
SynonymsNarcotine
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Contraindicated
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability~30%
Elimination half-life1.5 to 4h (mean 2.5)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC22H23NO7
Molar mass413.421
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.


Medical uses

Noscapine is often used as an antitussive medication.[1] A 2012 Dutch guideline; however, does not recommend its use for coughing.[2]

Side effects

Interactions

Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics.[3]

The drug should not be taken with any MAOIs (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.[citation needed]

Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased.[4]

Mechanism of action

Noscapine's antitussive effects appear to be primarily mediated by its σ–receptor agonist activity. Evidence for this mechanism is suggested by experimental evidence in rats. Pretreatment with rimcazole, a σ- specific antagonist, causes a dose-dependent reduction in antitussive activity of noscapine.[5]

Structure analysis

The lactone ring is unstable and opens in basic media. The opposite reaction is presented in acidic media. The bond C1-C3' is also unstable. This is the bond connecting the two optically active carbon atoms. In aqueous solution of sulfuric acid and heating it dissociates into cotarnine (4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline) and opic acid (6-formyl-2,3-dimethoxybenzoic acid). When noscapine is reduced with zinc/HCl, the bond C1-C3' saturates and the molecule dissociates into hydrocotarnine (2-hydroxycotarnine) and meconine (6,7-dimethoxyisobenzofuran-1(3H)-one).

History

Noscapine was first isolated and characterized in chemical breakdown and properties in 1817 under the denomination of "Narcotine"[6] by Pierre Robiquet, a French chemist in Paris. Robiquet conducted over 20 years between 1815 and 1835 a series of studies in the enhancement of methods for the isolation of morphine, and also isolated in 1832 another very important component of raw opium, that he called codeine, currently a widely used opium-derived compound.

Society and culture

Recreational use

There are anecdotal reports of the recreational use of over-the-counter drugs in several countries, being readily available from local pharmacies without a prescription. The effects, beginning around 45 to 120 mins after consumption, are similar to dextromethorphan and alcohol intoxication. Unlike dextromethorphan, noscapine is not an NMDA receptor antagonist.[7]

Noscapine in heroin

Noscapine can survive the manufacturing processes of heroin and can be found in street heroin. This is useful for law enforcement agencies, as the amounts of contaminants can identify the source of seized drugs. In 2005 in Liège, Belgium, the average noscapine concentration was around 8%.[8]

Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine.[9] Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in urine samples alongside noscapine include papaverine and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. Detection is performed by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry (LCMS) but can also use a variety of other analytical techniques.

Research

Noscapine is currently being investigated as an antitumor agent in animal models of several human cancers.

See also

  • Narceine, a lesser known but related opium alkaloid.

References

  1. ↑ Singh, H; Singh, P; Kumari, K; Chandra, A; Dass, SK; Chandra, R (March 2013). "A review on noscapine, and its impact on heme metabolism". Current drug metabolism. 14 (3): 351–60. PMID 22935070.
  2. ↑ Verlee, L; Verheij, TJ; Hopstaken, RM; Prins, JM; Salomé, PL; Bindels, PJ (2012). "[Summary of NHG practice guideline 'Acute cough']". Nederlands tijdschrift voor geneeskunde. 156 (0): A4188. PMID 22917039.
  3. ↑ Jasek, W, ed. (2007). Austria-Codex (in German) (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 978-3-85200-181-4.
  4. ↑ Template:Cite doi
  5. ↑ Kamei J (1996). "Role of opioidergic and serotonergic mechanisms in cough and antitussives". Pulmonary pharmacology. 9 (5–6): 349–356. doi:10.1006/pulp.1996.0046. PMID 9232674.
  6. ↑ Observations sur le mémoire de M. Sertuerner relatif à l’analyse de l’opium, Robiquet, Annales de Chimie et de Physique , volume 5 (1817), p275–278
  7. ↑ Church J, Jones MG, Davies SN, Lodge D (June 1989). "Antitussive agents as N-methylaspartate antagonists: further studies". Can. J. Physiol. Pharmacol. 67 (6): 561–7. doi:10.1139/y89-090. PMID 2673498.
  8. ↑ Denooz R, Dubois N, Charlier C (2005). "[Analysis of two year heroin seizures in the Liege area]". Revue médicale de Liège (in French). 60 (9): 724–8. PMID 16265967.
  9. ↑ Paterson S, Lintzeris N, Mitchell TB, Cordero R, Nestor L, Strang J (2005). "Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence". Addiction. 100 (12): 1832–1839. doi:10.1111/j.1360-0443.2005.01225.x. PMID 16367984.

Template:Cough and cold preparations

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