Morphine noscapine

Papaver somniferum (opium poppy) contains a variety of opioid and related alkaloids, including codeine, morphine, noscapine, papaverine, and thebaine. Crude opium is the air-dried latex obtained by incising the unripe capsules of P. somniferum. Paregoric is ammoniated tincture of opium (Scotch paregoric) or camphorated tincture of opium (English paregoric). The use of these formulations has largely been replaced by use of the purified compounds. 

Simultaneous acetylcodeine, benzocaine, cafTeine, cocaine, codeine, diamorphine, lido-caine, 6-monoacetylmorphine, morphine, noscapine, papaverine, procaine... 

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. 

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. 

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 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. 

The opium is obtained from the opium poppy Papaver somniferum. It contains two type of alkaloids e.g. phenanthrene derivatives (morphine, codeine thebaine) and benzyl isoquinoline derivatives (papaverine and noscapine). 

The opium alkaloids, which are obtained from Papaver somniferum, contain two groups of compounds compounds with phenanthrene derivatives, consisting of morphine, codeine, and thebaine and compounds with isoquinoline derivatives, consisting of papaverine and 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. 

OPIATE Drug derived directly from opium and used in its natural state, without chemical modification. Opiates include morphine, codeine, thebaine, noscapine, and papaverine. 

Opium is obtained from the dried juice from the seed capsule of the oriental poppy, Papaver somniferum. The dried juice contains up to 17% morphine and 4% codeine by weight, as well as other, non-additive alkaloids that lack analgesic activity such as noscapine, papaverine, and thebaine. Papaveretum is a standardized preparation of opium containing 50% morphine. 

There are at least 25 alkaloids of opium belonging to different chemical classes morphine (about 10 % of opium), noscapine or narcotine (about 5 %), papaverine (1 %), codeine (0.4 %), tebaine (0.4 %), narceine (0.2 %), but not all of these possess psychotropic effects. The illicit opiates may be natural molecules, such as morphine and codeine, and semisynthetic, such as heroin. Methadone and meperidine represent a group of totally synthetic molecules with opiate psychotropic effects. 

In the process of preparing a tincture, some pharmacologically active constituents of the plant are extracted by the alcohol. Although not all substances are soluble in alcohol, those that are include the alkaloids. In the case of a tincture of raw opium, the soluble alkaloids include morphine, codeine, noscapine, and papavarine. Such tinctures of opium were the infamous laudanum preparations of the late 1800s (see Appendix). 

Isolation of the alkaloids from the latex of the opium poppy, Papaver somniferum, led to the identification of over 20 compounds (Fig. 11.1). The most abundant alkaloids were morphine (1), codeine (2), thebaine (3), noscapine (4), and papaverine (5). 

Figure 8.1 MEKC of bulk heroin, heroin impurities, degradation products and adulterants. Conditions capillary, 25 cm X 50 mm i.d. voltage, 20 kV temperature, 40° C buffer, 85 mM SDS-8.5 mAf phosphate-8.5 mM borate-15% acetonitrile, pH 8.5 detector wavelength, 210 nm. Peaks b, morphine c, 3-MAM d, 6-MAM e, acetylcodeine f, heroin g, phenobarbital h, noscapine i, papaverine j, methaqua-lone. (From Weinberger and Lurie, 1991, with permission.)...

Another interesting aspect of this study was the comparison of MEKC and HPLC. While in MEKC the drugs represented in Figure 8.1 migrated in the order morphine (1), phenobarbital (2), 6-monoacetylmoprhine (6-MAM) (3), 3-monoacetyl morphine (3-MAM) (4), methaqualone (5), heroin (6), acetylcodeine (7), papaverine (8), and noscapine (9), in reversed-phase HPLC the elution pattern was substantially different and not correlated with MEKC... 

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