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Noscapine (also known as Narcotine or Anarcotine) is an alkaloid opioid agonist from plants of the Papaveraceae family, without significant painkilling properties. 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 (PDF file).

Structure analysis

Naturally it occurs as the alpha enantiomer. It can be converted into the beta enantiomer when it is dissolved in alkaline water-ethanol solutions. 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 sulphuric acid and heating it dissociates into Cortarnine (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 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 δ(Delta) & 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.

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.

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.

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 (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, and antihistamines) has been reported to cause chronic cough lasting over one month upon withdrawal. Unlike dextromethorphan, noscapine is not an NMDA receptor antagonist.

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%.

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

The effects shown above are not permanent; the user may experience spasms the following day after yawning.

WARNING: Do not take noscapine with any MAOIs (monoamine oxidase inhibitors), unknown and potentially fatal effects may occur. There are no significant contraindications listed for this drug but caution should be exercised.


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