| 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 |
| UNII | 8V32U4AOQU |
| KEGG | D01036 |
| ChEMBL | CHEMBL364713 |
| Synonyms | Narcotine |
| Chemical data | |
| Formula | C22H23NO7 |
| Mol. mass | 413.421 |
| SMILES | eMolecules & PubChem |
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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]
Contents |
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).
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).
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]
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.
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 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.
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.