Noscapine

Noscapine (Nectadon ), 2-methyl-8-methoxy-6,7-methylenedioxy-l-(6,7-di-methoxy-3-phtha-lidyl)-l,2,3,4-tetrahydroisoquinoline, is also one of the isoquinoline derivatives present in opium. Next to morphine, it is the most abundant of the opium alkaloids, present to the extent of 6% in the seed capsules. This drug was formerly known as narcotine but, because it is neither chemically nor pharmacologically related to the narcotics, is more appropriately designated as noscapine. 

Noscapine resembles papaverine in its action on smooth muscle and, in large doses, induces bronchodilation in animals. It is readily absorbed from the gastrointestinal tract, but its metabolic fate is unknown. In experimentally induced cough in animals and humans, noscapine exerts an antitussive action approximately equal to that of codeine, without any of the unpleasant side effects of codeine. It is administered orally in doses of 15 to 30 mg, three or four times daily as an antitussive. 

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Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Noscapine [128-62-1] (45) is the second most abundant alkaloid found in opium. Unlike most opium alkaloids, however, it has an isoquinoline rather than a phenanthrene ting system. Noscapine was first isolated in 1817 but its antitussive activity was not demonstrated pharmacologically until 1952 (63). Clinical studies have confirmed its effectiveness. It is not a narcotic and has a wide margin of safety when given orally. Death could be produced in rats only with doses > 800 mg/kg (64). Noscapine is isolated from the water-insoluble residue remaining after processing opium for the manufacture of morphine. 

How many mg each of noscapine and guaifenesin would be contained in each dose of the following prescription ... 

SM-)-Nicotine [54-11-5] Noscapine [128-62-1] 2541A I(3)1537B, N(2)647B QS5250000 RD2625000, USP... 

More than 30 alkaloids have been identified in opium (Robbers et al. 1996). The most relevant are morphine (4-21%), codeine (0.8-2.5%), noscapine (4-8%), papaverine (0.5-2.5%), and thebaine (0.5-2%) (figure 8.4). Other opium alkaloids include narceine, protopine, laudanine, codamine, cytopine, lanthopine, and meconidine. Numerous other opioids have been synthesized from opium alkaloids. Among them is heroin, or diacetylmorphine. 

Noscapine (107) Benzyl- CB3304 Oncology Tubulin binding Phase I/II Cougar 682-684,... 

Ye K, Ke Y, Keshava N, Shanks J, Kapp JA, Tekmal RR, Petros J, Joshi HC. (1998) Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells. Proc Natl Acad Sci USA 95 1601-1606. 

Aneja R, Dhiman N, Idnani J, Awasthi A, Arora SK, Chandra R, Joshi HC. (2007) Preclinical pharmacokinetics and bioavailability of noscapine, a tubulin-binding anticancer agent. Cancer Chemother Pharmacol 60 831-839. 

Jackson T, Chougule MB, Ichite N, Patlolla RR, Singh M. (2008) Antitumor activity of noscapine inhuman non-small cell lung cancer xenograft model. Cancer Chemother Pharmacol 63 117-126. 

Soaking plants parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i.e., basic substances of plant origin) including morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. 

The cough-suppressant (antitussive) effect produced by inhibition of the cough reflex is independent of the effects on nociception or respiration (antitussives codeine, noscapine). 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Cough may be dry or productive. A centrally acting cough suppressant can be tried in dry cough first choice treatment is noscapine which is safer and has less adverse reactions than codeine and ethyl morh-pine. 

Noscapine is a naturally occurring product of the opium poppy. It is a benzylisoquinoline with no analgesic or other CNS effects. Its antitussive effects are weak, but it is used in combination with other agents in mixtures for cough relief. 

As scientists began examining the nefarious poppy, they learned how to isolate opium s individual chemical entities. In 1804, a pharmacist from France named Derosyne first isolated what he thought to be the single essence of opium. At the time, it was believed that all of the effects of opium were caused by a single compound. But Derosyne had, in fact, discovered only one of the many chemicals in opium, noscapine. 

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