Chlorpromazine Metabolism II: Determination of Nonconjugated Metabolites in Blood of Schizophrenie Patients

Kaul, Pushkar N.; Conway, Michael W.; Ticku, Maharaj K.; Clark, Mervin L.

doi:10.1002/jps.2600610418

Cited by 13 publications

(3 citation statements)

References 6 publications

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“…The three drugs included in this study are known to undergo a variable degree of hydroxylation in the liver, via cytochrome-P450-dependent reactions; the main hydroxylated metabolites being p-hydroxyphenobarbital (Whyte & Dekaban 1977), 5-(4-hydroxyphenyl)-5-phenylhydantoin (Hoppel et al 1977;Perucca, Makki & Richens 1978) and 7-hydroxychlorpromazine (Kaul et al. 1972;Mackay, Healey & Baker 1974).…”

Section: Discussionmentioning

confidence: 99%

Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens

Wickramasinghe

1987

Clinical &Amp; Laboratory Haematology

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After interaction with human macrophages derived from blood, bone marrow or spleen, solutions of sodium phenobarbitone, phenytoin sodium and chlorpromazine hydrochloride showed reduced cytotoxicity towards K562 cells. The reduction in cytotoxicity was partially suppressed in the presence of tetrahydrofurane, an inhibitor of cytochrome P450. These data suggest that macrophages are capable of metabolizing certain drugs, probably via a cytochrome P450-dependent mechanism. The present findings raise the possibility that some drug-induced blood dyscrasias are caused by metabolism of the drug by bone marrow macrophages and the consequent release of relatively short-lived molecules which are toxic to adjacent haemopoietic cells. The generation of cytotoxic molecules during drug metabolism by macrophages may also be responsible for drug-induced damage to other macrophage-rich tissues. In addition, since cytochrome P450-dependent reactions seem to occur within macrophages, these cells may activate environmental procarcinogens and thus plays a role in carcinogenesis and leukaemogenesis.

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Section: Discussionmentioning

confidence: 99%

Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens

Wickramasinghe

1987

Clinical &Amp; Laboratory Haematology

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“…For flurazepam and its metabolites in blood and urine, the fluorometric procedure was based on hydrolysis to the benzophenones followed by K2CO3 cyclization to the 9acridanones (172). In the blood of schizophrenic patients, 11 chlorpromazine metabolites were quantitated as their DANSYL derivatives (439); the effects of pH, temperature, and solvent on the fluorescence of four phenothiazine derivatives were studied (671). A sensitive fluorometric method for protryptyline was found free of interference by other common psychiatric drugs (615).…”

Section: )mentioning

confidence: 99%

Fluorometric analysis

Weissler¹

1974

Anal. Chem.

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This review is dedicated to the memory of Prof. Charles E. White, who was at first the sole author and then the senior author of the 13 previous biennial reviews in this series. He was a leader in establishing the value and importance of fluorescence analysis; he was also a good and warm-hearted person, whose death in May 1973 was a real loss.were found to be very sensitive fluorescence reagents for detection of Zn, Al, Sc, Ga, and In, as well as suitable for quantitation of, for example, Zn at pH 6.9-7.2 in 80% EtOH (845). Acridine fluorescence quenching by iodine was proposed for the indirect determination of Au, Cr, Se,

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“…A comparison of the methods used before 1972 has been given by Usdin (2) (for chlorpromazine and its metabolites only) and by Cimbura (3). Current methods with sufficient sensitivity include mass fragmentography (4), electron capture-GLC (5)(6)(7), and fluorescent derivatization (8)(9)(10). All these methods have some disadvantages; mass fragmentography is far too complex and the equipment too expensive to be considered for general purposes, electron capture-GLC can only be used when halogen atoms are present, and fluorescent derivatization only permits the detection of metabolites containing primary amine or hydroxyl groups.…”

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confidence: 99%

Phosphorimetric analysis of phenothiazine derivatives

La¹,

Jn²,

Dl³

et al. 1975

Anal. Chem.

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No. 6 fuel oil measured at 80 and 20 K are compared in Figure 5. The major differences are increases in the intensities of the bands at 720 and 725 cm-1 at the lower temperature. These changes provide additional data for identifying petroleum; however, we do not feel that a couple of additional data values warrant the time and effort it takes to measure spectra at 20 K. Thus, we are confining our analyses to liquid N2 temperature.Results from this study indicate that low temperature infrared spectrometry can be used subsequent to room temperature infrared analysis for identifying petroleum products and petroleum pollution sources. The low temperature technique is only slightly more time consuming than room temperature analysis. Collaborating data from other analytical techniques will undoubtedly be needed in court cases; however, in spills where several similar oils are involved, infrared spectra measured at room temperature followed by measurements at 80 K provide convincing evidence for identifying the source. ACKNOWLEDGMENTWe express our appreciation to D. Eastwood for suggesting this study, and to A.

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Chlorpromazine Metabolism II: Determination of Nonconjugated Metabolites in Blood of Schizophrenie Patients

Cited by 13 publications

References 6 publications

Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens

Evidence of drug metabolism by macrophages: possible role of macrophages in the pathogenesis of drug-induced tissue damage and in the activation of environmental procarcinogens

Fluorometric analysis

Phosphorimetric analysis of phenothiazine derivatives

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