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Dopamine, serotonin and alpha-adrenergic receptor blocking activities in serum and their relationships to prolactin level in schizophrenic patients receiving long-term chlorpromazine treatment

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Abstract

The clinical application of a dopamine radioreceptor assay for neuroleptics has been proposed. Simultaneous monitoring of serum antidopaminergic (anti-DA), antiserotonergic (anti-5 HT) antiadrenergic (anti-NA) activities may provide a better understanding of clinical effects of neuroleptics. Serum anti-DA and anti-5 HT activities were estimated by competition for 3H-spiperone binding to dopamine and serotonin receptors in rat brain, respectively, and anti-NA activity by competition for 3H-WB-4101 binding to alphareceptors. Thirty-one patients receiving maintenance doses of chlorpromazine (CPZ) chronically were studied. Serum activitics varied among patients receiving the same dose, but correlated significantly with dose. Anti-DA activity also correlated with both anti-5 HT anti-NA activities, and the average ratio of anti-5 HT or anti-NA to anti-DA activity was slightly reduced by metabolism of CPZ. However, some patients had a different spectrum of serum activities from that of in vitro activities. Serum prolactin (PRL) correlated weakly with all the serum activities. The serum PRL anti-DA activity ratio appeared to be independent of anti-5 HT or anti-NA activity, suggesting the predominant involvement of anti-DA activity in the stimulation of PRL release.

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References

  • Calil HM, Avery DH, Hollister LE, Creese I, Snyder SH (1979) Serum levels of neuroleptics measured by dopamine radioreceptor assay and some clinical observations. Psychiat Res 1:39–44

    Google Scholar 

  • Cohen BM, Herschel M, Aoba A (1979) Neuroleptic, antimuscarinic, and antiadrenergic activity of chlorpromazine, thioridazine, and their metabolites. Psychiat Res 1:199–208

    Google Scholar 

  • Cohen BM, Lipinski JF, Harris PQ, Pope HG, Friedman M (1980a) Clinical use of the radioreceptor assay for neuroleptics. Psychiat Res 2:173–178

    Google Scholar 

  • Cohen BM, Lipinski JF, Pope HG, Harris PQ, Altesman RI (1980b) Neuroleptic blood levels and therapeutic effect. Psychopharmacology 70:191–193

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483

    Google Scholar 

  • Creese I, Snyder SH (1977) A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood. Nature 270:180–182

    Google Scholar 

  • Kamberi IA, Mical RA, Porter JC (1971) Effects of melatonin and serotonin on the release of FSH and prolactin. Endocrinology 88:1288–1293

    Google Scholar 

  • Kolakowska T, Wiles DH, Gelder MG, McNeilly AS (1976) Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving longterm phenothiazine treatment. Psychopharmacology 49:101–107

    Google Scholar 

  • Kolakowska T, Orr M, Gelder M, Heggie M, Wiles D, Franklin M (1979) Clinical significance of plasma drug and prolactin levels during acute chlorpromazine treatment: A replication study. Br J Psychiatry 135:352–359

    Google Scholar 

  • Leysen JE, Niemigeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272: 168–171

    Google Scholar 

  • Lu K-H, Meites J (1973) Effects of serotonin precursors and melatonin on serum prolactin release in rats. Endocrinology 93:152–155

    Google Scholar 

  • Mackay AVP, Healey AF, Baker J (1974) The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. Br J Clin Pharmacol 1:425–430

    Google Scholar 

  • Meltzer HY, Fang VS (1976) The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry 33:279–286

    Google Scholar 

  • Nakahara T, Kojima M, Uchimura H, Hirano M, Kim JS, Matsumoto T (1980) Interaction of oxypertine with rat brain monoamine receptors. Biochem Pharmacol 29:2681–2683

    Google Scholar 

  • Nakahara T, Hirano M, Uchimura H, Saito M, Kim JS, Matsumoto T, Mukai A, Nodomi A, Nakao H (1982) Antidopaminergic, antiserotonergic, and antiadrenergic activity of neuroleptics in serum of schizophrenic patients. In: Kaiya H, Namba M (eds) Psychobiology of schizophrenia. Pergamon, Oxford New York, pp 283–288

    Google Scholar 

  • Peroutka SJ, U'Prichard DC, Greenberg DA, Snyder SH (1977) Neuroleptic drug interactions with norepinephrine alpha-receptor binding sites in rat brain. Neuropharmacology 16:549–556

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. Am J Psychiatry 137:12:1518–1522

    Google Scholar 

  • Sakalis G, Chan TL, Gershon S, Park S (1973) The possible role of metabolites in therapeutic response to chlorpromazine treatment. Psychopharmacologia 32:279–284

    Google Scholar 

  • Sakurai Y, Nakahara T, Takahashi R (1975) Prediction of response to chlorpromazine treatment in schizophrenics. Psychopharmacologia 44:195–203

    Google Scholar 

  • Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261:717–719

    Google Scholar 

  • Tune LE, Creese I, Depaulo JR, Slavney PR, Coyle JT, Snyder SH (1980) Clinical state and serum neuroleptic levels measured by radioreceptor assay in schizophrenia. Am J Psychiatry 137:2:187–190

    Google Scholar 

  • Wode-Helgodt B, Alfredsson G (1981) Concentrations of chlorpro-mazine and two of its active metabolites in plasma and cerebrospinal fluid of psychotic patients treated with fixed drug doses. Psychopharmacology 73:55–62

    Google Scholar 

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Nakahara, T., Hirano, M., Uchimura, H. et al. Dopamine, serotonin and alpha-adrenergic receptor blocking activities in serum and their relationships to prolactin level in schizophrenic patients receiving long-term chlorpromazine treatment. Psychopharmacology 79, 266–270 (1983). https://doi.org/10.1007/BF00427825

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  • DOI: https://doi.org/10.1007/BF00427825

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