Noscapine

Noscapine

Systematic (IUPAC) name
(3S)- 6,7-Dimethoxy-3-[(5R)-5,6,7,8-tetrahydro- 4-methoxy- 6-methyl- 1,3-dioxolo (4,5-g)isoquinolin-5-yl]- 1(3H)-isobenzofuranone
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Bioavailability	~30%
Half-life	1.5 to 4h (mean 2.5)
Identifiers
CAS number	128-62-1
ATC code	R05DA07
PubChem	CID 275196
ChemSpider	242139 Y
UNII	8V32U4AOQU Y
KEGG	D01036 Y
ChEMBL	CHEMBL364713 Y
Synonyms	Narcotine
Chemical data
Formula	C22H23NO7
Mol. mass	413.421
SMILES	eMolecules & PubChem
InChI 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 Y Key:AKNNEGZIBPJZJG-MSOLQXFVSA-N Y
Y(what is this?)  (verify)

Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid from plants of the Papaveraceae family, without significant painkilling properties. This agent is primarily used for its antitussive (cough-suppressing) effects. It has also been shown to have anticancer activity. ^[1]

History

Noscapine was first isolated and characterized in chemical breakdown and properties in 1817 under the denomination of "Narcotine" ^[2] 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, today's probably most widely used opium-originating component).

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).

Mechanism of action

Noscapine's antitussive effects appear to be primarily mediated by its 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.^[3]

Cancer and stroke treatment

Noscapine is currently under investigation for use in the treatment of several cancers 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.^[4]

In stroke patients, noscapine blocks the bradykinine b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine.^[5]

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.

Abuse

Noscapine has a history of over-the-counter drug abuse 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.^[6]

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%.^[7]

Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine.^[8] 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.

Possible side-effects

• Loss of coordination
• Hallucinations (auditory and visual)
• Loss of sexual drive
• Swelling of prostate
• Loss of appetite
• Dilated pupils
• Increased heart rate
• Shaking and muscle spasms
• Chest pains
• Increased alertness
• Loss of any sleepiness
• Loss of stereoscopic vision

The effects shown above are not permanent.

Noscapine should not be taken with any MAOIs (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.

Noscapine should not be taken in conjunction with warfarin. The anticoagulant effects of warfarin are drastically increased by noscapine, leading to serious and possibly fatal thinning of the blood.

References

1. ^ "Cold med ingredient may treat prostate cancer". MSNBC. http://www.msnbc.msn.com/id/28470061/. Retrieved 2009-01-02. 
2. ^ 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
3. ^ 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. 
4. ^ "Noscapine effective against prostate cancer". http://www.news-medical.net/?id=21951. Retrieved 2007-07-16. 
5. ^ "A preliminary report on the application of noscapine in the treatment of stroke". http://www.springerlink.com/content/dlp6jd6gvrtgauk3/. Retrieved 2007-07-16. 
6. ^ PMID 2673498
7. ^ Denooz R, Dubois N, Charlier C (2005). "[Analysis of two year heroin seizures in the Liege area]" (in French). Revue médicale de Liège 60 (9): 724–8. PMID 16265967. 
8. ^ 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. 

External links

• [1]
• http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2291222 "Noscapine may increase the effects of warfarin"