Thebaine occurrence

In the plant family Papaveraceae, morphinane alkaloids were found only in some sections and species of the genus Papat er. The occurrence of thebaine was observed in the sections Orthorl oeades, Mecones, Pilosa, and Macrantha whereas morphine and codeine were found only in... 

The seasonal variations of the alkaloids and the areas of occurrence of F. officinalis and M. microcarpa have been studied (217, 839). A similar paper was devoted to P. somniferum (513, 840) an analysis revealed that a general accumulation of alkaloids, especially the hydrophenanthrene group, occurred one day after the flower had opened. This coincides with the peak of the pollination period. At that period, besides the principal opium poppy latex alkaloids (morphine, codeine, thebaine, papaverine, and narcotine), several other Dragendorff positive compounds were detected. The lysosomal property and accumulation of the alkaloids in vacuoles of Chelidonium majus have been described (841). 

Thebaine, the methoxy derivative of morphine, is also a habit-forming substance, but its primary toxic effects are similar to those of strychnine, a convulsant poison, rather than narcosis. Also, there are alkaloids having different structures but similar toxic actions. Lobeline, a lobelia alkaloid, which has a piperidine nucleus, shows pharmacologic action similar (but less potent) to that of nicotine, a tobacco alkaloid that has a pyridine-pyrrolidine ring system. The structure, occurrence, physical properties, and toxicity of some important alkaloids are presented in the following sections. 

A review of the cultivation of Papaver somniferum, and of its improvement and its utilization for medical purposes, has been published/ A method for the quantitative estimation of thebaine in P. bracteatum has been described and a study of the thebaine content of several strains of this poppy has been made. The occurrence of oripavine in P. orientale and of salutaridine in P. brac-teatum and P. lasiothrix has been reported. 

Phillipson JD, Handa SS, El-Dabbas SW (1976) N-Oxides of morphine, codeine and thebaine and their occurrence in Papaver species. Phytochemistry 19 1681-1684 Pummerer R, Puttfarcken H, Schopflocher P (1925) Oxidation of phenols. VIII. Dehydrogenation of p-cresol. Chem Ber 58B 1808-1820... 

Analysis of extracts obtained with cell cultures derived hom Papaver bracteatum and Papaver somniferum revealed the occurrence of thebaine in the former, of thebaine, codeine, and to a lesser extent of morphine in the latter material (Tables 1,2). Considering the many attempts to demonstrate morphinan alkaloids in cell cultures which remained unsuccessful and unreported, detection of occurrence would have been described until quite recently as a rare phenomenon. The availability of a radioimmunoassay and other improved analytical systems would explain the surge of reports of accumulation since 1980. According to recent analyses, concentrations of morphinan alkaloids are as low or lower than in leaf tissue (0.14% DW), and much lower than in dried latex, opium (ca. 20% DW). 

Callus and cell suspension cultures of opium poppy have, so far, not been seen to develop typical laticifers as displayed, for instance, in micrographs of shoots from seedlings and regenerants by Thureson-Klein (1970) and Nessler and Mahlberg (1977, 1979). Laticifer-like cells were demonstrated foxP. bracteatum cell cultures by Kut-chan et al. (1983). Absence of typical laticifers was often cited as the reason for failure to show occurrence of thebaine or codeine in poppy cell cultures. Today one may propose that accumulation of low amounts of morphinan alkaloids do not require latex and respective vessels. Indeed, other parts of the plant besides latex have... 

Conversely, alkaloid extracts were quite complex mixtures with sanguinarine as a major component. The predominance of benzophenanthridine, protopine and apor-phine alkaloids is common in cultured tissues of the Papaveraceae, despite their restricted occurrence in intact plants of this famfly (Ikuta et al. 1974, Kettenes-van den Bosch 1981, Phillipson 1983). HPLC was also used for the quantitation of these alkaloids and if preceded by fractionation on Extrelut columns (Roberts et al. 1983), the quantitation of thebaine was facilitated as well (Fig. lA). While sanguinarine was found in readily detectable amounts under a variety of growth conditions (Table 1), thebaine was discovered to be a trace constituent (Kutchan et al. 1983). Sanguinarine levels were highest in black aggregates that appeared by electron microscopic inspection to be necrotic tissue. These results suggest this benzophenanthridine alkaloid accumulates in mature, unidentified cells. 

Cytological investigation of P. bracteatum callus revealed the presence of parenchymal cells, with lesser numbers of meristematic and even fewer laticifer cells (Kutchan et al. 1983). Since the hormone-free media induced differentiation and an increase in the number of laticifer cells, an attempt to correlate morphinan alkaloid occurrence with that of laticifers was made. Seventeen different samples, from tissue containing only traces of thebaine, were inspected by light or electron microscopy and found to be devoid of such laticifer cells. Conversely, laticifer cells were encountered in elec-... 

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