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Metabolism of Phenothiazine and Butyrophenone Antipsychotic Drugs

A Review of some Recent Research Findings and Clinical Implications

Published online by Cambridge University Press:  06 August 2018

J. W. Hubbard ,
K. K. Midha ,
E. M. Hawes ,
G. McKAY ,
S. R. Marder ,
M. Aravagiri  and
E. D. Korchinski
J. W. Hubbard
Affiliation:
College of Pharmacy, University of Saskatchewan
K. K. Midha*
Affiliation:
Colleges of Pharmacy and Medicine, University of Saskatchewan and UCLA/Clinical Research Center for Schizophrenia & Psychiatric Rehabilitation, and the Psychopharmacology Laboratory, West Los Angeles Veteran's Affairs Medical Center
E. M. Hawes
Affiliation:
College of Pharmacy, University of Saskatchewan
G. McKAY
Affiliation:
College of Pharmacy, University of Saskatchewan
S. R. Marder
Affiliation:
UCLA/Clinical Research Center for Schizophrenia & Psychiatric Rehabilitation, and the Psychopharmacology Laboratory, West Los Angeles Veteran's Affairs Medical Center
M. Aravagiri
Affiliation:
UCLA/Clinical Research Center for Schizophrenia & Psychiatric Rehabilitation, and the Psychopharmacology Laboratory, West Los Angeles Veteran's Affairs Medical Center
E. D. Korchinski
Affiliation:
College of Pharmacy/Medicine, University of Saskatchewan
*
∗College of Pharmacy, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W0, Canada
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Abstract

Whereas some metabolites of antipsychotic drugs are psychoactive and contribute to clinical improvement, recent studies have provided evidence that certain metabolites contribute to side-effects which can be disabling enough to negate clinical improvement as regards the psychosis. The route of administration of the drug can determine the amount of metabolite produced in the body and affect how the patient feels in response to the treatment.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 163 , Issue S22: The Psychopharmacology of Schizophrenia , December 1993 , pp. 19 - 24
Copyright
Copyright © 1993 The Royal College of Psychiatrists 

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References

Altamura, A. C., Mauri, M. C., Cavallaro, R., et al (1987) Haloperidol metabolism and antipsychotic effect in schizophrenia. Lancet, i, 814–815.CrossRefGoogle Scholar
Bowen, W. D., Moses, E. L., Tolentino, P. J., et al (1990) Metabolites of haloperidol display preferential activity at sigma receptors compared to dopamine D-2 receptors. European Journal of Pharmacology, 177, 111–118.CrossRefGoogle ScholarPubMed
Chakraborty, B. S., Hubbard, J. W., Hawes, E. M., et al (1989) Interconversion between haloperidol and reduced haloperidol in healthy volunteers. European Journal of Clinical Pharmacology, 37, 45–48.Google Scholar
Chang, W.-H., Lin, S.-K. & Jann, M. W. (1991) Interconversions between haloperidol and reduced haloperidol in schizophrenic patients and guinea pigs: a steady state study. Journal of Clinical Psychopharmacology, 11, 99–105.Google Scholar
Chaudhary, A. K., Hubbard, J. W., McKay, G., et al (1988) Identification of a quaternary ammonium-linked glucuronide of chlorpromazine in the urine of a schizophrenic patient treated with chlorpromazine. Drug Metabolism and Disposition, 16, 506–508.Google Scholar
Ereshefsky, L., Davis, C. M., Harrington, C. A., et al (1984) Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients. Journal of Clinical Psychopharmacology, 4, 138–142.CrossRefGoogle ScholarPubMed
Forsman, A. & Larson, M. (1978) Metabolism of haloperidol. Current Therapy Research, 24, 567–568.Google ScholarPubMed
Jackson, C.-J. C., Hubbard, J. W., McKay, G., et al (1991a) Identification of phase I and phase II metabolites of fluphenazine in rat bile: intact glucuronide and sulfate conjugates. Drug Metabolism and Disposition, 19, 188–193.Google Scholar
Jackson, C.-J. C. & Hubbard, J. W., Midha, K. K. (19916) Biosynthesis and characterization of glucuronide metabolites of fluphenazine: 7-hydroxyfluphenazine glucuronide and fluphenazine glucuronide. Xenobiotica, 21, 383–393.CrossRefGoogle Scholar
Jann, M. W., Ereshefsky, L., Saklad, S. R., et al (1984) Haloperidol and reduced haloperidol plasma levels in schizophrenic patients. Drug Intelligence and Clinical Pharmacology, 18, 507.Google Scholar
Kirch, D. G., Palmer, M. R., Egan, M., et al (1985) Electrophysiological interactions between haloperidol and reduced haloperidol, and dopamine, norepinephrine and phencyclidine in rat brain. Neuropharmacology, 24, 375–379.Google Scholar
Korpi, E. R., Costakos, D. T. & Wyat, R. J. (1985) Interconversions of haloperidol and reduced haloperidol in guinea pig and rat liver microsomes. Biochemical Pharmacology, 34, 2923–2927.Google Scholar
Marder, S. R., Van Putten, T., Aravagiri, M., et al (1989) Plasma levels of parent drug and metabolites in patients receiving oral and depot fluphenazine. Psychopharmacology Bulletin, 25, 479–482.Google Scholar
Midha, K. K., Hawes, E. M., Hubbard, J. W., et al (1987) Interconversion between haloperidol and reduced haloperidol in humans. Journal of Clinical Psychopharmacology, 7, 363–364.CrossRefGoogle ScholarPubMed
Midha, K. K., Hawes, E. M., Hubbard, J. W., et al (1988) Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients. Psychopharmacology, 96, 206–211.Google Scholar
National Institute of Mental Health (1985) Rating scales and assessment instruments for use in pediatric psychopharmacology research. Psychopharmacology Bulletin, 21, 839–843.Google Scholar
Svendsen, C. N., Hrbek, C. C., Casendino, M., et al (1988) Concentration and distribution of thioridazine and metabolites in schizophrenic post-mortem brain tissue. Psychiatry Research, 23, 1–10.Google Scholar
Van Putten, T., Aravagiri, M., Marder, S. R., et al (1991) Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients. Psychopharmacology Bulletin, 27, 91–96.Google Scholar
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