Opium, alkaloids pharmacology

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. 

The Pharmacology of the Opium Alkaloids, by Krueger, Eddy and Sumwalt, which covers the period 1800 to 1942, and gives a comprehensive survey of pharmacological observations on the alkaloids of opium and their derivatives, with an exhaustive bibliography of over 10,000 titles. 

Linders, J.T.M., Kokje, J.P., Overhand, M., Lie, T.S. and Maat, L., Chemistry of opium alkaloids, Part XXV Diels-Alder reaction of 6-demethoxy-p-dihydrothebaine with methyl vinyl ketone using microwave heating preparation and pharmacology of 3-hydroxy-a, a, 17-trimethyl-6 3, 14 3-ethenomorphinan-7 3-methanol, a novel deoxygenated diprenorphine analog, Rec. des Trav. Chim. des Pays-Bas, 1988,107, 449. 

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. 

H Krueyer, N B Eddy, and M Sumwalt in The Pharmacology of the Opium Alkaloids, part 2, p 944, U S Government Printing Office, Washington, D C (1943)... 

Papaverine is an alkaloid present in opium, although it is not related chemically or pharmacologically to other opium alkaloids. It has a direct relaxant effect on smooth muscle, partly attributable to inhibition of phosphodiesterase. 

H. Krueger, N. B. Eddy, and Margaret Sumwalt, The Pharmacology of Opium Alkaloids, Part 2. Supplement No. 166 to the Public Health Reports, U. S. Government Printing OflGlce, Washington, D. C., 1943. 

Secondary metabolites are produced by plants in response to biotic or abiotic interactions with their environment and confer protection through a variety of antimicrobial, pesticidal, and pharmacological properties. Alkaloids are a class of plant secondary metabolites that traditionally have been classified as basic compounds derived firom amino acids that contain one or more heterocyclic nitrogen atom. About 20 % of plant species accumulate alkaloids, which are mostly derived from amino acids, e.g., phenylalanine, tyrosine, tryptophan, and lysine. The alkaloids are popular for their medicinal importance. The pharmaceutically important representatives of secondary metabolites are mostly alkaloids derived from tyrosine. In this chapter, we summarized the prior information, basic knowledge about the alkaloids, origin, physicochemical properties, uses, classification, biosynthetic reactions, and distribution of tyrosine-derived alkaloids especially opium alkaloids and their biosynthetic pathways in plants. We have also reviewed different web resources related to alkaloids and secondary metabolic pathway databases such as KEGG. 

Structure Activities and Pharmacological Properties of the Opium Alkaloids... 

In this report, a brief overview of the history of the chemistry and pharmacology of the opium alkaloids will be presented in order to place recent progress in opiate total synthesis in proper perspective. After a brief description of how past, present and possible future developments influenced the development of the NIH opiate total synthesis, some recent progress in this area will be described. 

Enkephalins and Endorphins. Morphine (142), an alkaloid found in opium, was first isolated in the early nineteenth century and widely used in patent medicines of that eta. It is pharmacologically potent and includes analgesic and mood altering effects. Endogenous opiates, the enkephalins, endorphins, and dynotphins were identified in the mid-1970s (3,51) (see Opioids, endogenous). Enkephalins and endorphins ate Hsted in Table 9. 

The synthesis of dextromethorphan is an outgrowth of early efforts to synthesize the morphine skeleton. /V-Methy1morphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-/V-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciUary activity, secretion of respiratory tract fluid, or respiration. 

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. 

---