Abstract
Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolacin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4–6 weeks on placebo and during 6–12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication.
Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.
Similar content being viewed by others
References
Andén, N.-E.: Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anticholinergic drugs. J. Pharm. Pharmacol. 24, 905–906 (1972)
Beumont, P. J. V., Corker, C. S., Friesen, H. G., Kolakowska, T., Mandelbrote, B. M., Marshall, J., Murray, M. A. F., Wiles, D. H.: The effects of phenothiazines on endocrine function: Effects in men and postmenopausal women. Brit. J. Psychiat. 124, 420–430 (1974)
Bowers, M. B.: 5 HIAA and HVA following probenecid in acute psychotic patients treated with phenothiazine. Psychopharmacologia (Berl.) 28, 309–318 (1973)
Bowers, M. B., Rositis, A.: Regional differences in homovanillic acid concentration after acute and chronic administration of antipsychotic drugs. J. Pharm. Pharmacol. 26, 743–745 (1974)
Curry, S. H.: Determination of nanogram quantities of chlorpromazine and some of its metabolites using gas liquid chromatography with an electron capture detector. Analyt. Chem. 40, 1251–1255 (1968)
Curry, S. H., Marshall, J. H. L.: Plasma levels of chlorpromazine and some of its relatively non-polar metabolites. Life Sci. 7, 9–17 (1968)
Curry, S. H., Marshall, J. H. L., Davis, J. M., Janowsky, D. S.: Chlorpromazine plasma levels and effects. Arch. gen. Psychiat. 22, 289–296 (1970)
Fyro, B. O., Wode-Helgodt, B., Borg, S., Sedvall, G.: The effect of chlorpromazine on homovanillic acid levels in cerebrospinal fluid of schizophrenic patients. Psychopharmacologia (Berl.) 35, 287–294 (1974)
Goodwin, F. K., Post, R. M., Sack, R. L.: Clinical evidence for neurochemical adaptation to psychotropic drugs. In: Neurobiological mechanisms of adaptation and behaviour. A. J. Mandell, ed., pp. 33–45. New York: Raven Press 1975
Harris, A. D., Letemendia, F. J. J., Willems, P. J. A.: A rating scale of the mental state: for use in the chronic population of psychiatric hospital. Brit. J. Psychiat. 113, 941–949 (1967)
Hwang, P., Gyuda, H., Friesen, H.: Radioimmunoassay of human prolactin. Proc. nat. Acad. Sci. (Wash.) 68, 1902–1906 (1971)
McNeilly, A. S., Hagen, C.: Prolactin, TSH, LH, and FSH responses in a combined LHRH/TRH test a different stages of the menstrual cycle. Clin. Endocr. 3, 427–435 (1974)
MacKay, A. V. P., Healey, A. F., Baker, J.: The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. Brit. J. Clin. Pharmacol. 1, 425–430 (1974)
O'Keeffe, R., Sharman, D. F., Vogt, M.: Effects of drugs used in psychoses on cerebral dopamine metabolism. Brit. J. Pharmacol. 38, 287–304 (1970)
Rivera-Calimlim, L., Castaneda, L., Lasagna, L.: Effects of mode of management of plasma chlorpromazine in psychiatric patients. Clin. Pharmacol. Ther. 14, 979–985 (1974)
Sakalis, G., Curry, S. H., Mould, G. O., Lader, M. H.: Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clin. Pharmacol. Ther. 13, 931–946 (1972)
Sayers, A. C., Burki, H. R., Ruch, W., Asper, H.: Neuroleptic induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesia. Effects of clozapine haloperidol, loxapine and chlorpromazine. Psychopharmacologia (Berl.) 41, 97–104 (1975)
Simpson, G. H., Angus, J. W. S.: A rating scale for extrapyramidal side-effects. Acta psychiat. scand. Suppl. 212, 11–19 (1970)
Wiesel, F. A., Alfredson, G., Likwornik, V., Sedvall, G.: A relation between drug concentration in brain and striatal homovanillic acid in chlorpromazine treated rats. Life Sci. 16, 1145–1156 (1975)
Wiles, D. H., Kolakowska, T., McNeilly, A. S., Mandelbrote, B. M., Gelder, M. G.: Clinical significance of plasma chlorpromazine levels: I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment. Psychol. Med. (in press, 1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kolakowska, T., Wiles, D.H., Gelder, M.G. et al. Clinical significance of plasma chlorpromazine levels. Psychopharmacology 49, 101–107 (1976). https://doi.org/10.1007/BF00427479
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00427479