[en] A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d₃) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d₀) was substituted by one dose of methadone-d₃ and plasma levels of methadone-d₀ and methadone-d₃ were followed for 48 h using a precise (SD +- 5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (tsub(1/2)) for both methadone-d₀ and methadone-d₃ were calculated from samples obtained 8-24 h following the dose of methadone-d₃. The tsub(1/2) of oral methadone-d₃ was shorter (22 +- 2 h) than that of methadone-d₀ (52 +- 20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body. (orig.) 891 AJ/orig. 892 MKO

[en] A synthesis of thebaine is described where the C-1 position is labelled with tritium to specific activity of 16 Ci/mmole. From codeine, 1-iodocodeine was prepared and converted to 1-iodothebaine in 3 steps. The subsequent key reaction was the selective hydrogenolysis of the carbon-iodine bond in 1-iodothebaine in the presence of the dienic-enol ether system. Using 10% Pd/C as catalyst, the desired reaction occurs in about 80% yield. (author)

[en] Identification of trace level of narcotic samples is required for various reasons. Of the different techniques available (such as GC-MS, surface ionization mass spectrometry, ESI-MS etc.,) for the detection of narcotics, ion mobility spectrometer (IMS) is widely used, as this can be made as portable instrument and hence easy for field deployable applications. In this paper, we present results on the detection of heroin, a representative of narcotics, using in-house developed IMS and MALDI instruments

No abstract available

[en] Morphine antibody purified by affinity chromatography was used to develop a solid-phase radioimmunoassay for morphine in polystyrene tubes. The tubes are coated with an appropriate concentration of the purified antibody, rinsed three times with buffered saline, and stored at -15⁰C. Using tritiated dihydromorphine, we determined competitive morphine binding by difference when the radioactivity in the assay supernates was measured after incubation (1 h, 37⁰C). Five standard curves, with use of serum equivalents of morphine ranging from 0 to 6 μg/liter, were linear and had a mean correlation coefficient of 0.98. Under conditions of the assay, levorphanol was comparable to morphine in its inhibitory effect on binding of labeled dihydromorphine, whereas dextrorphan was essentially inactive. Morphine-3-glucuronide, a major metabolite, is 55-fold less inhibitory in terms of its capacity to displace the radiolabel. We believe that the sensitivity of the technique, coupled with the simplicity of nonseparatory sampling, renders the system suitable for rapid determination of morphine and related compounds in biological fluids

[en] One of the best known side effects of using opium is spasm of the sphincter of Oddi, which may increase the diameter of the extrahepatic bile ducts. Ultrasound is the first imaging modality used for evaluating the biliary system because it is commonly available and noninvasive. The principal objective of this study was to measure the common bile duct (CBD) diameter via ultrasonography in opium addicts and to evaluate the relation between the CBD diameter and the period of addiction. This research was an analytical-cross sectional study that was done on 110 opium addicts that were admitted to a drug treatment center. The diameter of the CBD in these cases was measured by ultrasonography and the results were analyzed with other factors like age, the period of addiction and the laboratory findings. According to the findings, there is a significant increase in the range of the CBD diameter in comparison with normal bile ducts. Also, the mean diameter of the CBD in the different age groups showed a significant difference (p < 0.0001) and there was a significant relation between the CBD diameter and the period of addiction (p < 0.001, r = 0.74); so, with the increased length of the addiction period, the mean CBD diameter increases. Opium addiction is one of the factors that causes extrahepatic bile duct dilatation, so in these cases, if no obstructing lesion was found on ultrasound examination and the serum bilirobine and alkaline phosphatase levels are normal, then further evaluation is not needed

[en] The morphine derivatives N-p-azidophenylethyl-7,8-dihydronormorphine and its 7,8-ditritio analogue were synthesized from morphine. This material, a potential photoaffinity label with high specific radio-activity and with opiate agonist activity comparable to morphine, may be useful for labeling of opiate receptors. (author)

No abstract available

[en] It has recently been demonstrated that various forms of immune modification result in a profound attenuation of the opiate withdrawal syndrome. Herein we investigate the extent to which some of the immune modifiers active in withdrawal attenuation affect other opiate related behaviors, namely antinociception and the development of tolerance to this effect. The observations demonstrate that immune modification by cyclosporine and irradiation exposure result in an alteration of the acute antinociceptive effect of morphine; while none of these treatments modify the development of tolerance to this property of morphine. (Auth.)

[en] Highlights: • Opioids are important pain-relieving drugs but also carry a risk of harmful side effects. • Decreasing the pK_a of the opioid amine group promotes selective binding in inflamed tissue. • Fluorinated morphine derivatives are calculated to have lower pK_a’s for pH -specific binding. Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pK_a of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pK_a of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pK_a values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory by calculating the $\mathrm{\Delta }{\mathit{\text{G}}}_{\mathit{aq}}$ values for the amine deprotonation reactions.