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Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone or thiothixene

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Summary

Psychotic women with schizophrenic symptoms were treated with melperone 100 mg×3 (n=29) or thiothixene 10 mg×3 (n=34) using a double-blind procedure. Before and during treatment, levels of HVA, MOPEG, and 5-HIAA, the major metabolites of DA, NE, and 5-HT, were determined in lumbar cerebrospinal fluid by a mass fragmentographic technique. Both treatments resulted in an elevation of the HVA levels after 2 weeks, thiothixene having a more marked effect. The effect of thiothixene but not of melperone persisted after 4 weeks. Thiothixene did not influence the MOPEG level, but melperone reduced it after 4 weeks of treatment. The 5-HIAA levels were not significantly altered by the drugs. The HVA/MOPEG and the HVA/5-HIAA ratios were highly significantly elevated by both drugs after 2 as well as 4 weeks. Thiothixene induced a significantly greater change of these ratios than melperone. The results supply evidence that thiothixene accelerates central dopamine metabolism in man, presumably by blocking DA receptors. Melperone appears to act similarly, but has an effect which is weaker and/or of shorter duration. During long-term treatment with melperone the receptors develop tolerance to it. The acceleration in DA metabolism declines and the effect of melperone switches instead to central NA metabolism. The results indicate that both drugs cause long-term changes in the activity ratios of central monoamine systems. It is suggested that such changes in several systems rather than single biochemical events may be related to the antipsychotic effects of neuroleptic drugs. This study also demonstrated the versatility of using monoamine metabolite analysis of the CSF as a tool for the quantification of biochemical effects of neuroleptic drugs on the human CNS.

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Authors and Affiliations

  1. Laboratory of Experimental Psychiatry, Department of Psychiatry, Karolinska Institutet, S-10401, Stockholm, Sweden

    Lars Bjerkenstedt & Göran Sedvall

  2. Psychiatric Clinic 2, Beckomberga Hospital, S-16104, Bromma, Sweden

    Christer Härnryd

  3. Department of Statistics, University of Lund, S-22005, Lund, Sweden

    Bo Gullberg

Authors
  1. Lars Bjerkenstedt
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  2. Bo Gullberg
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  3. Christer Härnryd
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  4. Göran Sedvall
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Additional information

Financial support was provided by the Swedish Medical Research Council (14X-03560), National Institutes of Mental Health, (MH 27254-01), Bethesda, Maryland, USA, F. Hoffmann-La Roche & Co., Basle, Switzerland, Svenska Sällskapet för Medicinsk Forskning, Karolinska Institutet, AB Ferrosan, Sweden, and Pfizer-Roerig, Sweden.

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Bjerkenstedt, L., Gullberg, B., Härnryd, C. et al. Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone or thiothixene. Arch. Psychiat. Nervenkr. 224, 107–118 (1977). https://doi.org/10.1007/BF00346479

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