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Correlation Between Plasma Chlorpromazine and its Metabolites and Clinical Ratings in Patients with Acute Relapse of Schizophrenic and Paranoid Psychosis

Published online by Cambridge University Press:  29 January 2018

O. T. Phillipson ,
J. M. McKeown ,
J. Baker  and
A. F. Healey
O. T. Phillipson*
Affiliation:
MRC Neurochemical Pharmacology Unit, Department of Pharmacology, Cambridge
J. M. McKeown
Affiliation:
Fulbourn Hospital, Cambridge
J. Baker
Affiliation:
MRC Neurochemical Pharmacology Unit, Ida Darwin Hospital, Cambridge
A. F. Healey
Affiliation:
Clinical Chemistry Laboratory, Ida Darwin Hospital, Cambridge
*
Reprint requests and other correspondence to Dr Phillipson, Department of Anatomy, Karolinska Institute, S–104 01 Stockholm 60, Sweden.
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Abstract

Nine patients diagnosed as having acute schizophrenic psychosis were treated with chlorpromazine. Their clinical response to drug treatment was measured by the use of a clinical rating scale developed from the Present State Examination, and a nurses rating scale. Plasma levels of chlorpromazine (CPZ), 7-hydroxychlorpromazine (7OHCPZ), monodesmethylchlorpromazine (NOR1CPZ) and chlorpromazine sulphoxide (SOCPZ), were monitored during the period of hospital treatment. Correlations were made between the increase in plasma levels of drug or metabolites and improvement in the different PSE scores. These showed that the most significant correlations occurred when symptoms with high diagnostic significance for schizophrenia (Group 1) and symptoms rating perceptual disorders (P) were correlated with plasma 7OHCPZ levels in plasma samples taken before the first morning dose of CPZ. The ratio of 7OHCPZ to CPZ in these samples increased significantly as clinical ratings improved, this correlation being most highly significant against the Group 1 and P scores. The ratio of 7OHPCZ to SOCPZ increased significantly only in the case of Group 1 and P scores. This indicates a preferential shift of CPZ metabolism towards the formation of the active 7OHCPZ during the period of clinical improvement.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 131 , Issue 2 , August 1977 , pp. 172 - 184
Copyright
Copyright © Royal College of Psychiatrists 1977 

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References

Barry, III, Steenberg, M. L., Manian, A. A. & Buckley, J. P. (1974) Effects of chlorpromazine and three metabolites on behavioural responses in rats. Psycho-pharmacology (Berlin), 34, 351–60.Google Scholar
Bunney, B. S. & Aghajanian, G. K. (1974) Comparison of the effects of chlorpromazine and 7-hydroxychlorpromazine and chlorpromazine sulphoxide on the activity of central dopaminergic neurons. Life Sciences, 15, 309–18.Google Scholar
Burt, D. R., Enna, S. J., Creese, I. & Snyder, S. H. (1975) Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proceedings of the National Academy of Science, USA, 72, No. 11, 4655–9.Google Scholar
Chapman, J. (1966) The early symptoms of schizophrenia. British Journal of Psychiatry, 112, 225–51.Google Scholar
Coccia, P. F. & Westerfeld, W. W. (1967) The metabolism of chlorpromazine by liver microsomal enzyme systems. Journal of Pharmacology and Experimental Therapeutics, 157, 446.Google Scholar
Curry, S. H. (1968) Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma, using gas liquid chromatography with an electron capture detector. Analytical Chemistry, 40, 1251–5.Google Scholar
Curry, S. H., Marshall, J. H. L., Davies, J. M. & Janowsky, D. S. (1970) Chlorpromazine plasma levels and effects. Archives of General Psychiatry, 22, 289–96.Google Scholar
Curry, S. H. (1971) Chlorpromazine: concentrations in plasma excretion in urine and duration of effect. Proceedings of the Royal Society of Medicine, 64, 285–9.Google Scholar
Dailey, J., Sedvall, G. & Sjöquist, B. (1972) Effect of chlorpromazine and some of its metabolites on the accumulation of homovanillic acid in brain of mice. Journal of Pharmacy and Pharmacology, 24, 580.Google Scholar
Iversen, L. L. (1975) Dopamine receptors in the brain. Science, 188, 1084–9.Google Scholar
Lal, S. & Sourkes, T. L. (1972) Effects of various chlorpromazine metabolites on amphetamine induced stereotyped behaviour in the rat. European Journal of Pharmacology, 17, 283–6.CrossRefGoogle ScholarPubMed
Mackay, A. V. P., Healey, A. F. & Baker, J. (1974) The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. British Journal of Clinical Pharmacology, 1, 425–30.Google Scholar
Manian, A. A., Efron, D. H. & Goldberg, M. E. (1965) A comparative pharmacological study of a series of monohydroxylated and methoxylated chlorpromazine derivatives. Life Sciences, 4, 2425–38.Google Scholar
Marchbanks, G. & Williams, M. (1971) Factors affecting word selection by schizophrenic patients. British Journal of Social and Clinical Psychology, 10, 241–52.Google Scholar
Matthysse, S. (1973) Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Federation Proceedings, 32, 200–5.Google Scholar
Nybäck, H. & Sedvall, G. (1972) Effect of chlorpromazine and some of its metabolites on synthesis and turnover of catecholamines formed from 14C-tyrosine in mouse brain. Psychopharmacologia (Berlin), 26, 155–60.Google Scholar
Sakalis, G., Chan, T. L., Gershon, S. & Park, S. (1973) The possible role of metabolites in the therapeutic response to chlorpromazine treatment. Psychopharmacologia (Berlin), 32, 279–84.Google Scholar
Sakalis, G., Curry, S. H., Mould, G. P. & Lader, M. H. (1972) Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics, 13, 931–46.Google Scholar
Seemen, P., Chan-Wong, M., Fedesco, J. & Wong, K. (1975) Proceedings of the National Academy of Science. USA, 72, No. 11, 4376–80.Google Scholar
Snyder, S. H. (1972) Catecholamines in the brain as mediators of amphetamine psychosis. Archives of General Psychiatry, 27, 169–79.Google Scholar
Wing, I. K., Cooper, J. E. & Sartorius, N. (1972) The Measurement and Classification of Psychiatric Symptoms. Cambridge University Press.Google Scholar
Young, B. G. (1974) A phenomenological comparison of LSD and schizophrenic states. British Journal of Psychiatry, 124, 64–74.Google Scholar
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