Opium alkaloids. XI. Biosynthesis of aporphines in Papaver somniferum.
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The present study was designed to evaluate the effect of repeated oral administration of cryptopine at differential dosing regimens (50, 100, 150, 200 mg/kg bwt) in vivo on lipid peroxide measures, glutathione levels (GSH) and activity of glutathione S-transferase (GST) and glutathione reductase (GR) in the liver, spleen, kidney and lung of Male Wistar rats after a 5 day treatment period. In all the tissues examined, we observed an increase in lipid peroxidation and a decline in glutathione content and activity of glutathione S-transferase and glutathione reductase in a dose-dependent manner. The decrease in GSH content did not definitively correlate with a concomitant increase of lipid peroxidation in all the tissues. Our results ensemble that the enhancement of lipid peroxidation in the tissues investigated is a consequence of depletion of glutathione to certain critical levels and impairment of the glutathione-dependent enzyme systems viz. GST and GR. Our study potentiates that decreased levels of GSH may lead to lipid peroxidation, one of the key events in cellular damage. The inhibition of GST also suggests that the detoxification of the alkaloid could be suppressed following acute exposures. Conclusively, it appears that cryptopine in vivo disturbs the cellular defense system, so that it tips in the direction of autoxidative lipid peroxidation, producing cytotoxicity.
Thirty hair samples were collected from male opioid abusers for whom the presence of morphine in their urine samples was confirmed by thin layer chromatography (TLC). The hair samples were decontaminated by washing with isopropanol, deionized water, and isopropanol, dried at room temperature, and cut into small pieces. Samples of the latter (30 mg ) were digested by incubation in a mixture of methanol-trifluoroacetic acid (9:1) for 18 h at 45 degrees C and sonicated to improve the extraction process. The methanolic phase was evaporated to dryness under a stream of nitrogen at 50 degrees C. The sample was derivatized by addition of N-methyl- N-trimethylsilyltrifluoroacetamide (MSTFA) and 1% trimethyliodosilane (TMIS) at 70 degrees C for 20 min, with sonication. Derivatized samples (1 microL) were injected into a gas chromatograph-mass spectrometer (GC-MS) system fitted with a capillary column; the Finnigan MS was operated in SIM mode. Naltrexone was used as internal standard (IS). The masses of the ions selected for morphine and naltrexone were 429 and 557, respectively. The limit of quantitation was set at 0.03 ng mg(-1) hair. By using the above procedure we detected morphine in all the samples examined, in the concentration range 0.26-10.31 ng mg(-1 )hair.
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Opiate addicts are generally believed to consume a fairly constant level of drug. These data indicate that, for most addicts over time, there is considerable variability in dosage. This variability occurs not only amongst addicts, but also in most individual addicts over time. Extreme constancy in dosage does prevail for some addicts over prolonged periods, but this is not the norm. Factors influencing dosage include age, gender, ethnicity, socioeconomic status, duration of addiction, drug cost and drug availability. Distributions in dosage patterns are presented in this report.
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