Morphine, radioactive

It would be particularly desirable to produce nalline with a radioactive allyl group. Then studies should be made, with standard chemical and radioactivity techniques, of rates of excretion and degradation of nalline and morphine (radioactive methyl group) and the alterations in excretion and degradation of morphine when nalline is administered. The possibility of tracing either the nalline or the morphine separately should yield valuable information on the mechanism of action of both morphine and nalline. 

Table 4 gives the fractions of the original radioactivity recovered in the expired air, urine, and feces during given time intervals. However, the morphine radioactivity is continually destroyed and excreted, and the quan-... 

The conversion of reticuline (44) into morphinan alkaloids, which occurs with loss of tritium from C-1 in P. somniferum (see above)," has been observed also for the formation of thebaine (46) in P. bracteatum, a plant which produces this alkaloid but not codeine or morphine. Radioactive 1,2-dehydroreticuline (47) labelled both reticuline (44) and thebaine (46), whilst radioactive reticuline again labelled thebaine (46). ° Codeinone (48) and codeine (50) are biosynthetic intermediates between thebaine (46) and morphine (51) in P. somniferum, and it was shown that (48) was efficiently reduced to (50) in P. bracteatumf It is apparent that alkaloid biosynthesis in the two plants is similar, with the important difference that in P. bracteatum the enzymes which effect demethylation of (46) are missing, and so biosynthesis goes no further than thebaine (46). 

The washed-precipitate, containing antibody-bound morphine, is dissolved in NCS-solubilizer, and the radioactivity is counted with the help of a Packard-Iri-card Liquid Scintillation Spectrometer,... 

The tube which contained radioactive dihydromorphine and antiserum but no unlabelled morphine, served as a measure of maximum antibody-bound radioactivity,... 

Opioid receptors. Direct binding of highly radioactive opiates has permitted localization of specific opiate receptors of several types.863-866 The three major types (p, 8, k) are all 7-helix receptors coupled to adenylate cyclase, K+ and Ca2+ channels, and the MAP kinase cascade.866 The p receptors bind morphine most tightly.867 8673 These receptors are found in various cortical and subcortical regions of the brain. Most narcotics are polycyclic in nature and share the grouping indicated in Fig. 30-30. However, the flexible molecule methadone binds to the same receptors.868 Among antagonists that block the euphoric effects of opiates the most effective is naloxone (Fig. 30-30). 

Papaver Alkaloids.—Biosynthesis of morphine (36) occurs, in Papaver somniferum, through reticuline (33) by way of thebaine (35). The sequence from (35) to (36) involves, inter alia, two O-demethylations, with that at the methoxy-group at C-6 occurring first.1,2 Confirmation that the other methoxy-group is not demethylated first in this Papaver species obtains from the failure to detect oripavine (37), which is found in other Papaver species, as a natural constituent of P. somniferum. The experiment involved attempted isolation of radioactive (37), using inactive alkaloid as carrier, following a feeding experiment with radioactive reticuline (33).37... 

Effect of pH on the incorporation of cocaine, benzoylecgonine, and morphine into hair. Caucasian brown hair was exposed to the drug (5 pg/mL) containing a radioactive tracer in 10 mM phosphate buffer at the indicated pH for 1-h, The hair was rinsed three times with water and dried. A 30-min ethanol decontamination was followed by six phosphate decontamination washes. The hair was then digested with sodium hydroxide and the drug concentration measured by scintillation counting. 

Using spin labelled morphine it is possible to use ESR as an assay technique in this way for opium narcotics in urine and saliva, for antibodies derived from morphine are found to be also active against a number of related chemicals such as heroin and cocaine [164-166]. The absence of the possible hazards and inconveniences of radioactivity and the lack of a need to isolate the displaced molecules from those still bound to the antibody favour the spin immunoassay technique. The American army has been using this method of detection since 1972, and the measurement can be made in about 30 seconds. 

Actually, of course, a sense of security has nothing whatever to do with actual safety. For example, there s nothing like a good, solid lethal dose of morphine to make a man s worries and fears ease away. A cat might well curl up comfortably on a nice, warm mass of radioactive matter, thermally content while the gamma radiation tore it to pieces. 

Barton s approach was truly biomimetic, as it pursued an initially described conversion of labelled reticuline 76 to radioactive morphine 77, thus supporting the proposed biosynthetic route. Figure 10. 

Reduction to a mixture of the epimeric diols, followed by acid catalyzed allylic displacement by the phenolic group, yielded radioactive thebaine 81 and thus formalized "...a third and long sought synthesis of the morphine alkaloids...".50... 

Urinary excretion during the first 6 hr. accounted for 29-74 % of the injected morphine, and for 56-91 % at 24 hr. (see Table 5). Three of the 5 subjects excreted 5-7 % during the 2nd day and all excreted small amounts the 3rd day. The addict excreted morphine at the most rapid rate and had the greatest urine output. Nontolerant subjects excreted 7-10% of the dose in the feces in 3-4 days. In contrast, the feces of the addict contained only a negligible amount of radioactivity. 

EXCRETION OF RADIOACTIVITY AFTER ADMINISTRATION OF N C Ha-LABELED MORPHINE... 

During the periods 0 00-6 00, 6 00-12 00, and 12 00-24 00 hr. after the administration of the radioactive morphine to HE, 2.39%, 0.62%, and 0.36% of the injected activity were recovered from the expired air in the same intervals 55.96%, 8.72%, and 11.02% were recovered in the urine. Initially 23 times as much radioactivity appeared in the urine as in the expired air, while from 6 (X)-12 00 only 12 times as much, and in the final period 30 times as much radioactivity was obtained in the urine. 

FRACTIONAL RATES OF EXCRETION AND TURNOVER TIMES OF RESIDUAL RADIOACTIVITY AFTER THE ADMINISTRATION OF MORPHINE (100, 47a)... 

Urine. During the first 6 hr. after the administration of radioactive morphine, 71 % of the radioactivity was recovered in the urine of the addict FA. From 6 00-12 00,32 % of the remaining radioactivity appeared in the... 

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