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d-Cycloserine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label study

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Summary

D-cycloserine, a partial agonist at the strichnine-insensitive glycine site of the NMDA receptor complex, was tested as adjuvant treatment to conventional neuroleptics in chronic schizophrenic volunteers. The drug was administered, o.a.d., at the daily dose of 250 mg for six weeks. Mental status outcome measures were completed at the end of each week of treatment. The major finding was a deteriora of the patients' clinical condition, specifically of their psychotic symptoms. These preliminary results are discussed among others in view of d-cycloserine pharmacologic properties and recent findings on the interaction between NMDA agonists and dopamine system. This study, finally, suggests the need for a controlled dose-finding trial to establish the activity and a therapeutic “window” of this drug in schizophrenia.

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References

  • Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia-implications for schizophrenia and Parkinson's disease. Trends Neurosci 13: 272–276

    Google Scholar 

  • Carpenter WT, Buchanan RW (1989) Domains of psychopathology relevant to the study of etiology and treatment of schizophrenia. In: Schulz SC, Tamminga CA (eds) Schizophrenia: scientific progress. Oxford University Press, New York, pp 13–22

    Google Scholar 

  • Csernansky JG, Murphy GM, Faustmman WO (1991) Limbic/mesolimbic connections and the pathogenesis of schizophrenia. Biol Psychiatry 30: 383–400

    Google Scholar 

  • Emmett MR, Wood PL, Rao TS, Mick S, Cler JA, Iyengar S (1990) SC-49088 (D-cyclo-serine) a partial agonist at the NMDA-associated glycine receptor site in vivo. GD Searle & Co, BRD90D1522

    Google Scholar 

  • Hood WF, Compton RP, Monahan JB (1989) D-cycloserine: a ligand for the N-methyl-D-aspartate coupled glycine receptor has partial agonist properties. Neurosci Lett 98: 91–95

    Google Scholar 

  • Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148: 1301–1308

    Google Scholar 

  • Johnson SW, Seutin V, North AR (1992) Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump. Science 258: 665–667

    Google Scholar 

  • Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20: 379–382

    Google Scholar 

  • Kretschmer BD, Zado WB, Volz TL, Schmidt W (1992) The contribution of the different binding sites of the N-methyl-D-aspartate (NMDA) receptor to the expression of behavior. J Neural Transm [GenSect] 87: 23–34

    Google Scholar 

  • Luby ED, Gottlieb JS, Coehn BD, Rosenbaum G, Domino EF (1962) Model psychosis and schizophrenia. Am J Psychiatry 119: 61–65

    Google Scholar 

  • Macciardi F, Lucca A, Catalano M, Marino C, Zanardi R, Smeraldi E (1990) Amino acid patterns in schizophrenia: some new findings. Psychiatry Res 32: 63–70

    Google Scholar 

  • Quiron R, Bayorh MA, Zerbe RL, Pert CV (1984) Evidence for an endogenous peptide ligand for the phencyclidine receptor. Peptides 5: 967–973

    Google Scholar 

  • Rosse RB, Schwartz BL, Leighton MP, Davis RE, Deutsch SI (1990) An open-label trial of milacemide in schizophrenia: an NMDA intervention strategy. Clin Neuropharmacol 13: 348–354

    Google Scholar 

  • Tamminga CA, Cascella N, Fakouhi TD, Herting RL (1992) Enhancement of NMDA-mediated transmission in schizophrenia: effects of milacemide. In: Meltzer HY (ed) Novel antipsychotic drugs. Raven Press, New York, pp 171–178

    Google Scholar 

  • Watson GB, Bolanowski MA, Baganoff MP, Deppler CL, Lanthorn TH (1990) D-cyclo-serine acts as a partial agonist at the glycine modulatory site of the NMDA receptor expressed in Xenopus oocytes. Brain Res 510: 158–160

    Google Scholar 

  • Waziri R (1988) Glycine therapy of schizophrenia. Biol Psychiatry 23: 209–214

    Google Scholar 

  • Zukin SR, Zukin RS, Vale W (1987) An endogenous ligand of the brain sigma/PCP receptor antagonizes NMDA-induced neurotransmitter release. Brain Res 4/6: 84–89

    Google Scholar 

Download references

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Author notes

  1. N. G. Cascella

    Present address: CNS Department, Farmitalia Carlo Erba, Via Imbonati 24, I-20159, Milan, Italy

Authors and Affiliations

  1. Department of Neuropsychiatric Sciences, H. S. Raffaele, University of Milan, School of Medicine, Milan, Italy

    N. G. Cascella, F. Macciardi, C. Cavallini & E. Smeraldi

Authors
  1. N. G. Cascella
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  2. F. Macciardi
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  3. C. Cavallini
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  4. E. Smeraldi
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Cascella, N.G., Macciardi, F., Cavallini, C. et al. d-Cycloserine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label study. J. Neural Transmission 95, 105–111 (1994). https://doi.org/10.1007/BF01276429

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  • DOI: https://doi.org/10.1007/BF01276429

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