Noscapine

Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the Papaveraceae family. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its antitussive (cough-suppressing) effects. Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the Papaveraceae family. It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. 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 acute coughing. Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. The drug 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 as the anticoagulant effects of warfarin may be increased. 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. Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation The lactone ring is unstable and opens in basic media. The opposite reaction is presented in acidic media. The bond (C1−C3′) connecting the two optically active carbon atoms is also unstable. In aqueous solution of sulfuric acid and heating it dissociates into cotarnine (4-methoxy-6-methyl-5,6,7,8-tetrahydro-dioxoloisoquinoline) 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 was first isolated and characterized in chemical breakdown and properties in 1817 under the denomination of 'Narcotine' 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. 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 minutes after consumption, are similar to dextromethorphan and alcohol intoxication. Unlike dextromethorphan, noscapine is not an NMDA receptor antagonist.